407 results on '"Tan, Wen Hann"'
Search Results
2. Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS).
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Tjeertes, Jorrit, Bacino, Carlos, Bichell, Terry, Bustamante, Mariana, Crean, Rebecca, Jeste, Shafali, Komorowski, Robert, Krishnan, Michelle, Miller, Meghan, Nobbs, David, Ochoa-Lubinoff, Cesar, Parkerson, Kimberly, Rotenberg, Alexander, Sadhwani, Anjali, Shen, Mark, Squassante, Lisa, Tan, Wen-Hann, Vincenzi, Brenda, Wheeler, Anne, Hipp, Joerg, Berry-Kravis, Elizabeth, and Bird, Lynne
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Angelman syndrome ,Clinical outcome assessments ,Clinical trials ,Digital health technology ,EEG ,Endpoint development ,Natural history ,Sleep ,UBE3A ,Humans ,Angelman Syndrome ,Prospective Studies ,Pandemics ,COVID-19 ,Electroencephalography - Abstract
BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms. METHODS: Fifty-five individuals with AS (aged
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- 2023
3. Chromatinopathies – from discovery to clinical diagnosis in the real world
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Russell, Bianca E. and Tan, Wen-Hann
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- 2024
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4. Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III
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Sadhwani, Anjali, Wheeler, Anne, Gwaltney, Angela, Peters, Sarika U, Barbieri-Welge, Rene L, Horowitz, Lucia T, Noll, Lisa M, Hundley, Rachel J, Bird, Lynne M, and Tan, Wen-Hann
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Education ,Health Sciences ,Psychology ,Pediatric ,Rare Diseases ,Infant ,Child ,Humans ,Developmental Disabilities ,Motor Skills ,Angelman Syndrome ,Autism Spectrum Disorder ,Child Development ,Neurodevelopmental disorders ,Motor skills disorders ,Language development disorders ,Developmental disabilities ,Child development ,Psychology and Cognitive Sciences ,Developmental & Child Psychology ,Health sciences - Abstract
We describe the development of 236 children with Angelman syndrome (AS) using the Bayley Scales of Infant and Toddler Development, Third Edition. Multilevel linear mixed modeling approaches were used to explore differences between molecular subtypes and over time. Individuals with AS continue to make slow gains in development through at least age 12 years of age at about 1-2 months/year based on age equivalent score and 1-16 growth score points/year depending on molecular subtype and domain. Children with a deletion have lower scores at baseline and slower rate of gaining skills while children with UBE3A variant subtype demonstrated higher scores as well as greater rates of skill attainment in all domains. The developmental profiles of UPD and ImpD were similar.
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- 2023
5. Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III
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Sadhwani, Anjali, Wheeler, Anne, Gwaltney, Angela, Peters, Sarika U., Barbieri-Welge, Rene L., Horowitz, Lucia T., Noll, Lisa M., Hundley, Rachel J., Bird, Lynne M., and Tan, Wen-Hann
- Abstract
We describe the development of 236 children with Angelman syndrome (AS) using the Bayley Scales of Infant and Toddler Development, Third Edition. Multilevel linear mixed modeling approaches were used to explore differences between molecular subtypes and over time. Individuals with AS continue to make slow gains in development through at least age 12 years of age at about 1-2 months/year based on age equivalent score and 1-16 growth score points/year depending on molecular subtype and domain. Children with a deletion have lower scores at baseline and slower rate of gaining skills while children with "UBE3A" variant subtype demonstrated higher scores as well as greater rates of skill attainment in all domains. The developmental profiles of UPD and ImpD were similar.
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- 2023
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6. Adaptive Skills of Individuals with Angelman Syndrome Assessed Using the Vineland Adaptive Behavior Scales, 2nd Edition
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Gwaltney, Angela, Potter, Sarah Nelson, Peters, Sarika U., Barbieri-Welge, Rene L., Horowitz, Lucia T., Noll, Lisa M., Hundley, Rachel J., Bird, Lynne M., Tan, Wen-Hann, Sadhwani, Anjali, and Wheeler, Anne
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- 2023
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7. DNA methylation signature associated with Bohring-Opitz syndrome: a new tool for functional classification of variants in ASXL genes
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Awamleh, Zain, Chater-Diehl, Eric, Choufani, Sanaa, Wei, Elizabeth, Kianmahd, Rebecca R, Yu, Anna, Chad, Lauren, Costain, Gregory, Tan, Wen-Hann, Scherer, Stephen W, Arboleda, Valerie A, Russell, Bianca E, and Weksberg, Rosanna
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Human Genome ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Animals ,Craniosynostoses ,DNA Methylation ,Epigenesis ,Genetic ,Humans ,Intellectual Disability ,Mammals ,Syndrome ,Transcription Factors ,Clinical Sciences ,Genetics & Heredity - Abstract
The additional sex combs-like (ASXL) gene family-encoded by ASXL1, ASXL2, and ASXL3-is crucial for mammalian development. Pathogenic variants in the ASXL gene family are associated with three phenotypically distinct neurodevelopmental syndromes. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes show consistent patterns of genome-wide DNA methylation (DNAm) alterations, i.e., DNAm signatures in peripheral blood. Given the role of ASXL1 in chromatin modification, we hypothesized that pathogenic ASXL1 variants underlying Bohring-Opitz syndrome (BOS) have a unique DNAm signature. We profiled whole-blood DNAm for 17 ASXL1 variants, and 35 sex- and age-matched typically developing individuals, using Illumina's Infinium EPIC array. We identified 763 differentially methylated CpG sites in individuals with BOS. Differentially methylated sites overlapped 323 unique genes, including HOXA5 and HOXB4, supporting the functional relevance of DNAm signatures. We used a machine-learning classification model based on the BOS DNAm signature to classify variants of uncertain significance in ASXL1, as well as pathogenic ASXL2 and ASXL3 variants. The DNAm profile of one individual with the ASXL2 variant was BOS-like, whereas the DNAm profiles of three individuals with ASXL3 variants were control-like. We also used Horvath's epigenetic clock, which showed acceleration in DNAm age in individuals with pathogenic ASXL1 variants, and the individual with the pathogenic ASXL2 variant, but not in individuals with ASXL3 variants. These studies enhance our understanding of the epigenetic dysregulation underpinning ASXL gene family-associated syndromes.
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- 2022
8. Anxiety in Angelman Syndrome.
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Grebe, Stacey, Limon, Danica, McNeel, Morgan, Guzick, Andrew, Peters, Sarika, Tan, Wen-Hann, Sadhwani, Anjali, Bacino, Carlos, Samaco, Rodney, Berry, Leandra, Goodman, Wayne, Schneider, Sophie, Storch, Eric, and Bird, Lynne
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Angelman syndrome ,anxiety ,children ,developmental behavior checklist ,Adolescent ,Adult ,Angelman Syndrome ,Anxiety ,Caregivers ,Checklist ,Child ,Humans ,Neurodevelopmental Disorders - Abstract
Angelman Syndrome (AS) is a neurodevelopmental disorder most commonly caused by the impaired expression of the maternal UBE3A gene on chromosome 15. Though anxiety has been identified as a frequently present characteristic in AS, there are limited studies examining anxiety in this population. Studies of anxiety in other neurodevelopmental disorders have found disorder specific symptoms of anxiety and age specific displays of anxiety symptoms. However, there is a consistent challenge in identifying anxiety in people with neurodevelopmental disorders given the lack of measurement instruments specifically designed for this population. Given the limited information about AS and anxiety, the aims of the current project were to (a) examine symptoms of anxiety in children with AS and (b) determine the correlates of anxiety in children with AS. Participants included 42 adult caregivers of youth with AS in the AS Natural History study who completed the Developmental Behavior Checklist (DBC). The results found that 26% of the sample demonstrated elevated symptoms of anxiety and established a relationship between elevated anxiety in youth with AS and higher levels of irritability, hyperactivity, self-absorbed behaviors, and disruptive/antisocial behaviors. Findings from this research provide a foundation for tailoring evidence-based assessments and treatments for youth with AS and anxiety.
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- 2022
9. Clinical Characterization of Epilepsy in Children With Angelman Syndrome.
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Cassater, Daiana, Bustamante, Mariana, Sach-Peltason, Lisa, Rotenberg, Alexander, Nespeca, Mark, Tan, Wen-Hann, Hipp, Joerg, and Bird, Lynne
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15q11-13 ,Angelman syndrome ,Epilepsy ,GABA ,GABR ,Genotype ,Seizures ,UBE3A ,Adolescent ,Angelman Syndrome ,Child ,Child ,Preschool ,Epilepsy ,Female ,Follow-Up Studies ,Genotype ,Humans ,Infant ,Infant ,Newborn ,Male ,Retrospective Studies - Abstract
BACKGROUND: Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design. METHODS AND MATERIALS: We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype. RESULTS: Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P
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- 2021
10. Evaluating Sleep Disturbances in Children With Rare Genetic Neurodevelopmental Syndromes
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Veatch, Olivia J, Malow, Beth A, Lee, Hye-Seung, Knight, Aryn, Barrish, Judy O, Neul, Jeffrey L, Lane, Jane B, Skinner, Steven A, Kaufmann, Walter E, Miller, Jennifer L, Driscoll, Daniel J, Bird, Lynne M, Butler, Merlin G, Dykens, Elisabeth M, Gold, June-Anne, Kimonis, Virginia, Bacino, Carlos A, Tan, Wen-Hann, Kothare, Sanjeev V, Peters, Sarika U, Percy, Alan K, and Glaze, Daniel G
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Neurosciences ,Lung ,Pediatric ,Rare Diseases ,Behavioral and Social Science ,Intellectual and Developmental Disabilities (IDD) ,Genetics ,Mental Health ,Clinical Research ,Sleep Research ,Neurodegenerative ,Brain Disorders ,Adolescent ,Angelman Syndrome ,Child ,Child ,Preschool ,Humans ,Neurodevelopmental Disorders ,Prader-Willi Syndrome ,Rett Syndrome ,Sleep Wake Disorders ,Pediatric sleep ,Rare disease ,Genetic syndromes ,Neurodevelopment ,Paediatrics and Reproductive Medicine ,Neurology & Neurosurgery ,Paediatrics - Abstract
BackgroundAdequate sleep is important for proper neurodevelopment and positive health outcomes. Sleep disturbances are more prevalent in children with genetically determined neurodevelopmental syndromes compared with typically developing counterparts. We characterize sleep behavior in Rett (RTT), Angelman (AS), and Prader-Willi (PWS) syndromes to identify effective approaches for treating sleep problems in these populations. We compared sleep-related symptoms across individuals with these different syndromes with each other, and with typically developing controls.MethodsChildren were recruited from the Rare Diseases Clinical Research Network consortium registries; unaffected siblings were enrolled as related controls. For each participant, a parent completed multiple sleep questionnaires including Pediatric Sleep Questionnaire (Sleep-Disordered Breathing), Children's Sleep Habits Questionnaire (CSHQ), and Pediatric Daytime Sleepiness Scale.ResultsSleep data were analyzed from 714 participants, aged two to 18 years. Young children with AS had more reported sleep problems than children with RTT or PWS. Older children with RTT had more reported daytime sleepiness than those with AS or PWS. Finally, all individuals with RTT had more evidence of sleep-disordered breathing when compared with individuals with PWS. Notably, typically developing siblings were also reported to have sleep problems, except for sleep-related breathing disturbances, which were associated with each of the genetic syndromes.ConclusionsIndividuals with RTT, AS, and PWS frequently experience sleep problems, including sleep-disordered breathing. Screening for sleep problems in individuals with these and other neurogenetic disorders should be included in clinical assessment and managements. These data may also be useful in developing treatment strategies and in clinical trials.
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- 2021
11. Electrophysiological Abnormalities in Angelman Syndrome Correlate With Symptom Severity
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Hipp, Joerg F, Frohlich, Joel, Keute, Marius, Tan, Wen-Hann, and Bird, Lynne M
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Medical Physiology ,Biomedical and Clinical Sciences ,Mental Health ,Neurodegenerative ,Epilepsy ,Behavioral and Social Science ,Pediatric ,Clinical Research ,Brain Disorders ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Neurological - Abstract
BackgroundAngelman syndrome (AS) is a rare neurodevelopmental disorder caused by the absence of functional UBE3A in neurons. Excess low-frequency oscillations as measured with electroencephalography (EEG) have been identified as a characteristic finding, but the relationship of this EEG finding to the symptomatology of AS and its significance in the pathophysiology of AS remain unknown.MethodsWe used correlations and machine learning to investigate the cross-sectional and longitudinal relationship between EEG spectral power and motor, cognitive, and language skills (Bayley Scales of Infant and Toddler Development, Third Edition); adaptive behavior (Vineland Adaptive Behavior Scales, Second Edition); AS-specific symptoms (AS Clinical Severity Scale); and the age of epilepsy onset in a large sample of children (age: 1-18 years) with AS due to a chromosomal deletion of 15q11-q13 (45 individuals with 72 visits).ResultsWe found that after accounting for age differences, participants with stronger EEG delta-band abnormality had earlier onset of epilepsy and lower performance scores across symptom domains including cognitive, motor, and communication. Combing spatial and spectral information beyond the delta frequency band increased the cross-sectional association with clinical severity on average by approximately 45%. Furthermore, we found evidence for longitudinal correlations of EEG delta-band power within several performance domains, including the mean across Bayley Scales of Infant and Toddler Development, Third Edition, scores.ConclusionsOur results show an association between EEG abnormalities and symptom severity in AS, underlining the significance of the former in the pathophysiology of AS. Furthermore, our work strengthens the rationale for using EEG as a biomarker in the development of treatments for AS, a concept that may apply more generally to neurodevelopmental disorders.
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- 2021
12. Health-related quality of life and medication use among individuals with Angelman syndrome
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Khan, Nasreen, Cabo, Raquel, Burdine, Rebecca D., Tan, Wen-Hann, Keary, Christopher J., Ochoa-Lubinoff, Cesar, and Bird, Lynne M.
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- 2023
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13. Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment
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Keute, Marius, Miller, Meghan T, Krishnan, Michelle L, Sadhwani, Anjali, Chamberlain, Stormy, Thibert, Ronald L, Tan, Wen-Hann, Bird, Lynne M, and Hipp, Joerg F
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Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Neurosciences ,Behavioral and Social Science ,Clinical Research ,Pediatric ,Rare Diseases ,Intellectual and Developmental Disabilities (IDD) ,Human Genome ,Mental Health ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Angelman Syndrome ,Chromosomes ,Human ,Pair 15 ,Genomic Imprinting ,Genotype ,Humans ,Phenotype ,Ubiquitin-Protein Ligases ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - Abstract
Angelman Syndrome (AS) is a severe neurodevelopmental disorder due to impaired expression of UBE3A in neurons. There are several genetic mechanisms that impair UBE3A expression, but they differ in how neighboring genes on chromosome 15 at 15q11-q13 are affected. There is evidence that different genetic subtypes present with different clinical severity, but a systematic quantitative investigation is lacking. Here we analyze natural history data on a large sample of individuals with AS (n = 250, 848 assessments), including clinical scales that quantify development of motor, cognitive, and language skills (Bayley Scales of Infant Development, Third Edition; Preschool Language Scale, Fourth Edition), adaptive behavior (Vineland Adaptive Behavioral Scales, Second Edition), and AS-specific symptoms (AS Clinical Severity Scale). We found that clinical severity, as captured by these scales, differs between genetic subtypes: individuals with UBE3A pathogenic variants and imprinting defects (IPD) are less affected than individuals with uniparental paternal disomy (UPD); of those with UBE3A pathogenic variants, individuals with truncating mutations are more impaired than those with missense mutations. Individuals with a deletion that encompasses UBE3A and other genes are most impaired, but in contrast to previous work, we found little evidence for an influence of deletion length (class I vs. II) on severity of manifestations. The results of this systematic analysis highlight the relevance of genomic regions beyond UBE3A as contributing factors in the AS phenotype, and provide important information for the development of new therapies for AS. More generally, this work exemplifies how increasing genetic irregularities are reflected in clinical severity.
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- 2021
14. Gaboxadol in angelman syndrome: A double-blind, parallel-group, randomized placebo-controlled phase 3 study
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Keary, Christopher, Bird, Lynne M., de Wit, Marie-Claire, Hatti, Shivkumar, Heimer, Gali, Heussler, Helen, Kolevzon, Alexander, Mathews, Adera, Ochoa-Lubinoff, Cesar, Tan, Wen-Hann, Yan, Ying, and Adams, Maxwell
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- 2023
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15. The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome
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Bird, Lynne M, Ochoa-Lubinoff, Cesar, Tan, Wen-Hann, Heimer, Gali, Melmed, Raun D, Rakhit, Amit, Visootsak, Jeannie, During, Matthew J, Holcroft, Christina, Burdine, Rebecca D, Kolevzon, Alexander, and Thibert, Ronald L
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Patient Safety ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adolescent ,Adult ,Angelman Syndrome ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Drug Administration Schedule ,Female ,GABA Agonists ,Humans ,Isoxazoles ,Male ,Middle Aged ,Treatment Outcome ,Young Adult ,Clinical Sciences ,Neurosciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo evaluate safety and tolerability and exploratory efficacy end points for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS).MethodsGaboxadol is a highly selective orthosteric agonist that activates δ-subunit-containing extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd), gaboxadol 10 mg morning dose and 15 mg evening dose (bid), or placebo morning and evening dose. Safety and tolerability were monitored throughout the study. Prespecified exploratory efficacy end points included adapted Clinical Global Impression-Severity and Clinical Global Impression-Improvement (CGI-I) scales, which documented the clinical severity at baseline and change after treatment, respectively.ResultsEighty-eight individuals were randomized. Of 87 individuals (aged 13-45 years) who received at least 1 dose of study drug, 78 (90%) completed the study. Most adverse events (AEs) were mild to moderate, and no life-threatening AEs were reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006).ConclusionAfter 12 weeks of treatment, gaboxadol was found to be generally well-tolerated with a favorable safety profile. The efficacy as measured by the AS-adapted CGI-I scale warrants further studies.Clinicaltrialsgov identifierNCT02996305.Classification of evidenceThis study provides Class I evidence that, for individuals with AS, gaboxadol is generally safe and well-tolerated.
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- 2021
16. AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia
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Terhal, Paulien, Venhuizen, Anton J., Lessel, Davor, Tan, Wen-Hann, Alswaid, Abdulrahman, Grün, Regina, Alzaidan, Hamad I., von Kroge, Simon, Ragab, Nada, Hempel, Maja, Kubisch, Christian, Novais, Eduardo, Cristobal, Alba, Tripolszki, Kornelia, Bauer, Peter, Fischer-Zirnsak, Björn, Nievelstein, Rutger A.J., van Dijk, Atty, Nikkels, Peter, Oheim, Ralf, Hahn, Heidi, Bertoli-Avella, Aida, Maurice, Madelon M., and Kornak, Uwe
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- 2023
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17. A dyadic approach to the delineation of diagnostic entities in clinical genomics
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Biesecker, Leslie G, Adam, Margaret P, Alkuraya, Fowzan S, Amemiya, Anne R, Bamshad, Michael J, Beck, Anita E, Bennett, James T, Bird, Lynne M, Carey, John C, Chung, Brian, Clark, Robin D, Cox, Timothy C, Curry, Cynthia, Dinulos, Mary Beth Palko, Dobyns, William B, Giampietro, Philip F, Girisha, Katta M, Glass, Ian A, Graham, John M, Gripp, Karen W, Haldeman-Englert, Chad R, Hall, Bryan D, Innes, A Micheil, Kalish, Jennifer M, Keppler-Noreuil, Kim M, Kosaki, Kenjiro, Kozel, Beth A, Mirzaa, Ghayda M, Mulvihill, John J, Nowaczyk, Malgorzata JM, Pagon, Roberta A, Retterer, Kyle, Rope, Alan F, Sanchez-Lara, Pedro A, Seaver, Laurie H, Shieh, Joseph T, Slavotinek, Anne M, Sobering, Andrew K, Stevens, Cathy A, Stevenson, David A, Tan, Tiong Yang, Tan, Wen-Hann, Tsai, Anne C, Weaver, David D, Williams, Marc S, Zackai, Elaine, and Zarate, Yuri A
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Rare Diseases ,Genetics ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Genetic Diseases ,Inborn ,Genomics ,Genotype ,Humans ,Mutation ,Phenotype ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
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- 2021
18. Anxiety in Angelman Syndrome
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Grebe, Stacey C., Limon, Danica L., McNeel, Morgan M., Guzick, Andrew, Peters, Sarika U., Tan, Wen-Hann, Sadhwani, Anjali, Bacino, Carlos A., Bird, Lynne M., Samaco, Rodney C., Berry, Leandra N., Goodman, Wayne K., Schneider, Sophie C., and Storch, Eric A.
- Abstract
Angelman Syndrome (AS) is a neurodevelopmental disorder most commonly caused by the impaired expression of the maternal "UBE3A" gene on chromosome 15. Though anxiety has been identified as a frequently present characteristic in AS, there are limited studies examining anxiety in this population. Studies of anxiety in other neurodevelopmental disorders have found disorder specific symptoms of anxiety and age specific displays of anxiety symptoms. However, there is a consistent challenge in identifying anxiety in people with neurodevelopmental disorders given the lack of measurement instruments specifically designed for this population. Given the limited information about AS and anxiety, the aims of the current project were to: (1) examine symptoms of anxiety in children with AS; and (2) determine the correlates of anxiety in children with AS. Participants included 42 adult caregivers of youth with AS in the AS Natural History study who completed the Developmental Behavior Checklist (DBC). The results found that 26% of the sample demonstrated elevated symptoms of anxiety and established a relationship between elevated anxiety in youth with AS and higher levels of irritability, hyperactivity, self-absorbed behaviors, and disruptive/antisocial behaviors. Findings from this research provide a foundation for tailoring evidence-based assessments and treatments for youth with AS and anxiety.
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- 2022
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19. An observational study of pediatric healthcare burden in Angelman syndrome: results from a real-world study
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Khan, Nasreen, Cabo, Raquel, Tan, Wen-Hann, Tayag, Regina, and Bird, Lynne M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Rare Diseases ,Health Services ,Pediatric ,Quality Education ,Angelman Syndrome ,Child ,Child ,Preschool ,Health Care Costs ,Humans ,Infant ,Healthcare economics ,Healthcare resource utilization ,Rare disease ,Disease burden ,Other Medical and Health Sciences ,Genetics & Heredity ,Genetics ,Clinical sciences - Abstract
BACKGROUND:The objective of this study is to describe variations in the healthcare resource utilization (HRU) among individuals with Angelman syndrome (AS) over the first 12 years of life. Data for this study were drawn from the AS Natural History study (ASNHS), which is an observational study on the developmental progress, behavior, and medical morbidity of individuals with AS conducted over eight years. Caregiver-reported information on hospitalization, surgery, and medication utilization was used to assess HRU. Repeated measures mixed effect models were used to assess the relationship between age and probability of hospitalization, surgery, and prescription medication utilization. RESULTS:Mean age at study enrollment was 6 years of age and both sexes were equally represented. The mean number of visits per participant was three. Results from this study suggest that individuals with AS have a high HRU burden. Hospitalization and surgery burden were highest in the first year of life. Use of medications for seizures and sleep disturbance increased over time. CONCLUSIONS:The study highlights the significant healthcare burden among individuals with AS. Future studies that estimate cost and caregiver burden associated with AS are needed to assess the lifelong economic impact of AS on families and healthcare system.
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- 2019
20. Healthcare burden among individuals with Angelman syndrome: Findings from the Angelman Syndrome Natural History Study
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Khan, Nasreen, Cabo, Raquel, Tan, Wen‐Hann, Tayag, Regina, and Bird, Lynne M
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Biological Sciences ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Genetics ,Brain Disorders ,Patient Safety ,Angelman Syndrome ,Child ,Child ,Preschool ,Delivery of Health Care ,Female ,Hospitalization ,Humans ,Length of Stay ,Male ,Patient Acceptance of Health Care ,Registries ,Retrospective Studies ,United States ,healthcare burden ,healthcare costs ,healthcare resource utilization ,medical economics ,supportive therapy utilization ,Clinical Sciences ,Medicinal and biomolecular chemistry - Abstract
BackgroundThe objective of this study is to describe healthcare resource utilization (HRU) and supportive therapy utilization (STU) among individuals with Angelman syndrome (AS), and to compare such usage by molecular etiology.MethodsParticipants were categorized into deletion and non-deletion genotypes. Statistical differences were assessed using an independent samples t test.ResultsData were available on 302 individuals. Mean age of participants was 5.5 years, 92% of whom were less than 13 years, and 71% had the deletion etiology. About 68% of participants had at least one hospitalization since birth to enrollment in the study; the average number of hospitalizations during that time period was 2.3 and average length of stay was 4.5 days. The most common reasons for hospitalization were seizures, lower respiratory infections, and surgery. The most common reasons for surgery were myringotomy, strabismus surgery, tonsillectomy or adenoidectomy, and gastrostomy tube insertion/fundoplication. Anticonvulsants, gastroesophageal reflux disease, sleep, and behavioral medications were the most commonly prescribed drugs. STU was high among individuals with AS.ConclusionsThis study shows that individuals with AS have high HRU/STU, and apart from a few differences, HRU/STU was similar across molecular etiology. These results reflect usage in younger individuals and studies that describe HRU/STU in older individuals are needed.
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- 2019
21. Maladaptive behaviors in individuals with Angelman syndrome
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Sadhwani, Anjali, Willen, Jennifer M, LaVallee, Nicole, Stepanians, Miganush, Miller, Hillary, Peters, Sarika U, Barbieri‐Welge, Rene L, Horowitz, Lucia T, Noll, Lisa M, Hundley, Rachel J, Bird, Lynne M, and Tan, Wen‐Hann
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Paediatrics ,Biomedical and Clinical Sciences ,Basic Behavioral and Social Science ,Clinical Research ,Behavioral and Social Science ,Mental Health ,Pediatric Research Initiative ,Pediatric ,Clinical Trials and Supportive Activities ,Adolescent ,Adult ,Alleles ,Angelman Syndrome ,Child ,Child ,Preschool ,Disease Susceptibility ,Female ,Genetic Predisposition to Disease ,Genotype ,Humans ,Infant ,Male ,Parenting ,Quality of Life ,Severity of Illness Index ,Stereotyped Behavior ,Stress ,Psychological ,Young Adult ,behavior rating scale ,behavioral symptoms ,developmental disabilities ,problem behavior ,Genetics ,Clinical Sciences ,Clinical sciences - Abstract
Maladaptive behaviors are challenging and a source of stress for caregivers of individuals with Angelman Syndrome (AS). There is limited information on how these maladaptive behaviors vary over time among individuals with AS due to different genetic etiologies. In this study, caregivers of 301 individuals with AS were asked questions about their child's behavior and completed the Aberrant Behavior Checklist-Community version (ABC-C). Developmental functioning was evaluated with either the Bayley Scales of Infant Development, Third Edition (Bayley-III) or the Mullen Scales of Early Learning (MSEL). Family functioning was assessed using the parent-completed Parenting Stress Index (PSI) and the Family Quality of Life questionnaire (FQoL). Approximately 70% of participants had AS due to a deletion on the maternally-inherited copy of chromosome 15q11q13. Results revealed that at baseline, individuals with AS had low scores in the domains of lethargy (mean: 2.6-4.2 depending on genotype) and stereotypy (mean: 2.3-4.2 depending on genotype). Higher cognitive functioning was associated with increased irritability (r = 0.32, p
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- 2019
22. Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes
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Frohlich, Joel, Miller, Meghan T, Bird, Lynne M, Garces, Pilar, Purtell, Hannah, Hoener, Marius C, Philpot, Benjamin D, Sidorov, Michael S, Tan, Wen-Hann, Hernandez, Maria-Clemencia, Rotenberg, Alexander, Jeste, Shafali S, Krishnan, Michelle, Khwaja, Omar, and Hipp, Joerg F
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Medical Physiology ,Biomedical and Clinical Sciences ,Neurosciences ,Mental Health ,Genetics ,Human Genome ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Angelman Syndrome ,Beta Rhythm ,Brain Waves ,Cerebral Cortex ,Child ,Child ,Preschool ,Delta Rhythm ,Electroencephalography ,Genotype ,Humans ,Infant ,Phenotype ,Theta Rhythm ,Angelman syndrome ,Biomarkers ,EEG ,GABA ,GABRB3-GABRA5-GABRG3 gene cluster ,UBE3A ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biological sciences ,Biomedical and clinical sciences ,Psychology - Abstract
BACKGROUND:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions of the gene UBE3A or deletion of chromosome 15 at 15q11-q13, which encompasses UBE3A and several other genes, including GABRB3, GABRA5, GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (β3, α5, γ3). Individuals with deletions are generally more impaired than those with other genotypes, but the underlying pathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesis that genes other than UBE3A located on 15q11-q13 cause differences in pathophysiology between AS genotypes. METHODS:We compared spectral power of clinical EEG recordings from children (1-18 years of age) with a deletion genotype (n = 37) or a nondeletion genotype (n = 21) and typically developing children without Angelman syndrome (n = 48). RESULTS:We found elevated theta power (peak frequency: 5.3 Hz) and diminished beta power (peak frequency: 23 Hz) in the deletion genotype compared with the nondeletion genotype as well as excess broadband EEG power (1-32 Hz) peaking in the delta frequency range (peak frequency: 2.8 Hz), shared by both genotypes but stronger for the deletion genotype at younger ages. CONCLUSIONS:Our results provide strong evidence for the contribution of non-UBE3A neuronal pathophysiology in deletion AS and suggest that hemizygosity of the GABRB3-GABRA5-GABRG3 gene cluster causes abnormal theta and beta EEG oscillations that may underlie the more severe clinical phenotype. Our work improves the understanding of AS pathophysiology and has direct implications for the development of AS treatments and biomarkers.
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- 2019
23. Methylation analysis and developmental profile of two individuals with Angelman syndrome due to mosaic imprinting defects
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Baker, Emma K., Merton, Catherine F., Tan, Wen-Hann, Dudding-Byth, Tracy, Godler, David E., and Sadhwani, Anjali
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- 2022
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24. A randomized controlled trial of levodopa in patients with Angelman syndrome
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Tan, Wen‐Hann, Bird, Lynne M, Sadhwani, Anjali, Barbieri‐Welge, Rene L, Skinner, Steven A, Horowitz, Lucia T, Bacino, Carlos A, Noll, Lisa M, Fu, Cary, Hundley, Rachel J, Wink, Logan K, Erickson, Craig A, Barnes, Gregory N, Slavotinek, Anne, Jeremy, Rita, Rotenberg, Alexander, Kothare, Sanjeev V, Olson, Heather E, Poduri, Annapurna, Nespeca, Mark P, Chu, Hillary C, Willen, Jennifer M, Haas, Kevin F, Weeber, Edwin J, and Rufo, Paul A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,Clinical Research ,Brain Disorders ,Prevention ,Pediatric ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Angelman Syndrome ,Animals ,Biomarkers ,Calcium ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Disease Models ,Animal ,Humans ,Levodopa ,Long-Term Potentiation ,Mice ,Neuropsychological Tests ,Treatment Outcome ,calcium-calmodulin-dependent protein kinase type 2 ,clinical trial ,developmental disabilities ,inborn genetic diseases ,rare disease ,UBE3A ,Genetics ,Clinical sciences - Abstract
Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi-center double-blind randomized placebo-controlled 1-year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1-year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1-year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well-tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.
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- 2018
25. Defining the phenotypic spectrum of SLC6A1 mutations
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Johannesen, Katrine M, Gardella, Elena, Linnankivi, Tarja, Courage, Carolina, Martin, Anne Saint, Lehesjoki, Anna‐Elina, Mignot, Cyril, Afenjar, Alexandra, Lesca, Gaetan, Abi‐Warde, Marie‐Thérèse, Chelly, Jamel, Piton, Amélie, Merritt, J Lawrence, Rodan, Lance H, Tan, Wen‐Hann, Bird, Lynne M, Nespeca, Mark, Gleeson, Joseph G, Yoo, Yongjin, Choi, Murim, Chae, Jong‐Hee, Czapansky‐Beilman, Desiree, Reichert, Sara Chadwick, Pendziwiat, Manuela, Verhoeven, Judith S, Schelhaas, Helenius J, Devinsky, Orrin, Christensen, Jakob, Specchio, Nicola, Trivisano, Marina, Weber, Yvonne G, Nava, Caroline, Keren, Boris, Doummar, Diane, Schaefer, Elise, Hopkins, Sarah, Dubbs, Holly, Shaw, Jessica E, Pisani, Laura, Myers, Candace T, Tang, Sha, Tang, Shan, Pal, Deb K, Millichap, John J, Carvill, Gemma L, Helbig, Kathrine L, Mecarelli, Oriano, Striano, Pasquale, Helbig, Ingo, Rubboli, Guido, Mefford, Heather C, and Møller, Rikke S
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Behavioral and Social Science ,Neurodegenerative ,Neurosciences ,Genetics ,Epilepsy ,Clinical Research ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Adolescent ,Adult ,Anticonvulsants ,Ataxia ,Child ,Child ,Preschool ,Cohort Studies ,Electroencephalography ,Epilepsies ,Myoclonic ,Epilepsies ,Partial ,Epilepsy ,Generalized ,Female ,GABA Plasma Membrane Transport Proteins ,Genetic Association Studies ,Humans ,Intellectual Disability ,Language Development Disorders ,Male ,Mutation ,Mutation ,Missense ,Neurodevelopmental Disorders ,Phenotype ,Treatment Outcome ,Valproic Acid ,Young Adult ,epilepsy ,epilepsy genetics ,MAE ,SLC6A1 ,MAE ,SLC6A1 ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
ObjectivePathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.MethodsWe collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.ResultsCognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).SignificanceMost patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
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- 2018
26. De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability
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Küry, Sébastien, van Woerden, Geeske M, Besnard, Thomas, Onori, Martina Proietti, Latypova, Xénia, Towne, Meghan C, Cho, Megan T, Prescott, Trine E, Ploeg, Melissa A, Sanders, Stephan, Stessman, Holly AF, Pujol, Aurora, Distel, Ben, Robak, Laurie A, Bernstein, Jonathan A, Denommé-Pichon, Anne-Sophie, Lesca, Gaëtan, Sellars, Elizabeth A, Berg, Jonathan, Carré, Wilfrid, Busk, Øyvind Løvold, van Bon, Bregje WM, Waugh, Jeff L, Deardorff, Matthew, Hoganson, George E, Bosanko, Katherine B, Johnson, Diana S, Dabir, Tabib, Holla, Øystein Lunde, Sarkar, Ajoy, Tveten, Kristian, de Bellescize, Julitta, Braathen, Geir J, Terhal, Paulien A, Grange, Dorothy K, van Haeringen, Arie, Lam, Christina, Mirzaa, Ghayda, Burton, Jennifer, Bhoj, Elizabeth J, Douglas, Jessica, Santani, Avni B, Nesbitt, Addie I, Helbig, Katherine L, Andrews, Marisa V, Begtrup, Amber, Tang, Sha, van Gassen, Koen LI, Juusola, Jane, Foss, Kimberly, Enns, Gregory M, Moog, Ute, Hinderhofer, Katrin, Paramasivam, Nagarajan, Lincoln, Sharyn, Kusako, Brandon H, Lindenbaum, Pierre, Charpentier, Eric, Nowak, Catherine B, Cherot, Elouan, Simonet, Thomas, Ruivenkamp, Claudia AL, Hahn, Sihoun, Brownstein, Catherine A, Xia, Fan, Schmitt, Sébastien, Deb, Wallid, Bonneau, Dominique, Nizon, Mathilde, Quinquis, Delphine, Chelly, Jamel, Rudolf, Gabrielle, Sanlaville, Damien, Parent, Philippe, Gilbert-Dussardier, Brigitte, Toutain, Annick, Sutton, Vernon R, Thies, Jenny, Peart-Vissers, Lisenka ELM, Boisseau, Pierre, Vincent, Marie, Grabrucker, Andreas M, Dubourg, Christèle, Network, Undiagnosed Diseases, Tan, Wen-Hann, Verbeek, Nienke E, Granzow, Martin, Santen, Gijs WE, Shendure, Jay, Isidor, Bertrand, Pasquier, Laurent, Redon, Richard, Yang, Yaping, State, Matthew W, Kleefstra, Tjitske, Cogné, Benjamin, HUGO, GEM, Study, Deciphering Developmental Disorders, Petrovski, Slavé, and Retterer, Kyle
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Neurosciences ,Brain Disorders ,Genetics ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Underpinning research ,1.1 Normal biological development and functioning ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Animals ,Brain ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Cell Line ,Exome ,Female ,Glutamic Acid ,HEK293 Cells ,Humans ,Intellectual Disability ,Male ,Mice ,Mice ,Inbred C57BL ,Mutation ,Neurons ,Phosphorylation ,Signal Transduction ,Undiagnosed Diseases Network ,GEM HUGO ,Deciphering Developmental Disorders Study ,AMPAR ,CAMK2 ,CAMK2A ,CAMK2B ,NMDAR ,de novo mutations ,intellectual disability ,synaptic plasticity ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.
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- 2017
27. MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway
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Gong, Maolei, primary, Li, Jiayi, additional, Liu, Yijun, additional, Matheus, Vernet Machado Bressan Wilk, additional, Li, Qian, additional, Liu, Haoran, additional, Liang, Chen, additional, Joel A, Morales-Rosado, additional, Cohen, Ana S.A., additional, Hughes, Susan S., additional, Sullivan, Bonnie R, additional, Waddell, Valerie, additional, Henriette van den Boogaard, Marie Jose, additional, van Jaarsveld, Richard H., additional, Binsbergen, Ellen van, additional, van Gassen, Koen L, additional, Wang, Tianyun, additional, Hiatt, Susan M., additional, Amaral, Michelle D., additional, Kelley, Whitley V., additional, Zhao, Jianbo, additional, Feng, Weixing, additional, Ren, Changhong, additional, Yu, Yazhen, additional, Boczek, Nicole J, additional, Ferber, Matthew J., additional, Lahner, Carrie, additional, Elliott, Sherr, additional, Ruan, Yiyan, additional, Mignot, Cyril, additional, Keren, Boris, additional, Xie, Hua, additional, Wang, Xiaoyan, additional, Popp, Bernt, additional, Zweier, Christiane, additional, Piard, Juliette, additional, Coubes, Christine, additional, Tran-Mau-Them, Frederic, additional, Safraou, Hana, additional, Innes, Micheil, additional, Gauthier, Julie, additional, Michaud, Jacques L, additional, Koboldt, Daniel C., additional, Sylvie, ODENT, additional, Willems, Marjolaine, additional, Tan, Wen-Hann, additional, Cogne, Benjamin, additional, Rieubland, Claudine, additional, Braun, Dominique, additional, McLean, Scott Douglas, additional, Platzer, Konrad, additional, Zacher, Pia, additional, Oppermann, Henry, additional, Evenepoel, Lucie, additional, BLANC, Pierre, additional, Khattabi, Laila El, additional, Haque, Neshatul, additional, Dsouza, Nikita R., additional, Zimmermann, Michael T, additional, Urrutia, Raul A, additional, Klee, Eric W, additional, Shen, Yiping, additional, Du, Hong-Zhen, additional, Qin, Zailong, additional, Liu, Chang-Mei, additional, and chen, xiaoli, additional
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- 2024
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28. The ER Thioredoxin-Related Transmembrane Protein TMX2 Controls Redox-Mediated Tethering of ER-Mitochondria Contacts (ERMCS)
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Chen, Junsheng, primary, Yap, Megan C, additional, Bassot, Arthur, additional, Pascual, Danielle M, additional, Makio, Tadashi, additional, Zimmermann, Jannik, additional, Mast, Heather, additional, Bhat, Rakesh, additional, Fleury, Samuel G, additional, Fan, Yuxiang, additional, Zardini Buzatto, Adriana, additional, Moore, Jack, additional, Ballanyi, Klaus, additional, Li, Liang, additional, Overduin, Michael, additional, Lemieux, M Joanne, additional, Lemieux, Helene, additional, Tan, Wen-Hann, additional, Mancini, Grazia M. S., additional, Morgan, Bruce, additional, Marcogliese, Paul C., additional, and Simmen, Thomas, additional
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- 2024
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29. Imprinted genes in clinical exome sequencing: Review of 538 cases and exploration of mouse-human conservation in the identification of novel human disease loci
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Bhoj, Elizabeth J., Rajabi, Farrah, Baker, Samuel W., Santani, Avni, and Tan, Wen-Hann
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- 2020
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30. Expansion of phenotype and genotypic data in CRB2-related syndrome
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Lamont, Ryan E, Tan, Wen-Hann, Innes, A Micheil, Parboosingh, Jillian S, Schneidman-Duhovny, Dina, Rajkovic, Aleksandar, Pappas, John, Altschwager, Pablo, DeWard, Stephanie, Fulton, Anne, Gray, Kathryn J, Krall, Max, Mehta, Lakshmi, Rodan, Lance H, Saller, Devereux N, Steele, Deanna, Stein, Deborah, Yatsenko, Svetlana A, Bernier, François P, and Slavotinek, Anne M
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Kidney Disease ,Clinical Research ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Renal and urogenital ,Adaptor Proteins ,Signal Transducing ,Carrier Proteins ,Cytoskeletal Proteins ,Female ,Genotype ,Humans ,Hydrocephalus ,Infant ,Intracellular Signaling Peptides and Proteins ,Male ,Membrane Proteins ,Mutation ,Nephrosis ,Pedigree ,Phenotype ,Proteins ,Syndrome ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype.
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- 2016
31. Proposed criteria for nevoid basal cell carcinoma syndrome in children assessed using statistical optimization
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Gold, Nina B., Campbell, Ian M., Sheppard, Sarah E., and Tan, Wen-Hann
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- 2021
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32. De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy
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Singh, Sakshi, Gupta, Aditi, Zech, Michael, Sigafoos, Ashley N., Clark, Karl J., Dincer, Yasemin, Wagner, Matias, Humberson, Jennifer B., Green, Sarah, van Gassen, Koen, Brandt, Tracy, Schnur, Rhonda E., Millan, Francisca, Si, Yue, Mall, Volker, Winkelmann, Juliane, Gavrilova, Ralitza H., Klee, Eric W., Engleman, Kendra, Safina, Nicole P., Slaugh, Rachel, Bryant, Emily M., Tan, Wen-Hann, Granadillo, Jorge, Misra, Sunita N., Schaefer, G. Bradley, Towner, Shelley, Brilstra, Eva H., and Koeleman, Bobby P. C.
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- 2020
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33. Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination
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Nakayama, Tojo, Al-Maawali, Almundher, El-Quessny, Malak, Rajab, Anna, Khalil, Samir, Stoler, Joan M, Tan, Wen-Hann, Nasir, Ramzi, Schmitz-Abe, Klaus, Hill, R Sean, Partlow, Jennifer N, Al-Saffar, Muna, Servattalab, Sarah, LaCoursiere, Christopher M, Tambunan, Dimira E, Coulter, Michael E, Elhosary, Princess C, Gorski, Grzegorz, Barkovich, A James, Markianos, Kyriacos, Poduri, Annapurna, and Mochida, Ganeshwaran H
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Biochemistry and Cell Biology ,Bioinformatics and Computational Biology ,Genetics ,Biological Sciences ,Neurosciences ,Human Genome ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Clinical Research ,Congenital Structural Anomalies ,Rare Diseases ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Generic health relevance ,Amino Acid Transport Systems ,Acidic ,Antiporters ,Female ,Genotype ,Hereditary Central Nervous System Demyelinating Diseases ,Homozygote ,Humans ,Male ,Microcephaly ,Mitochondrial Diseases ,Mutation ,Phenotype ,Psychomotor Disorders ,Pyrroline Carboxylate Reductases ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Despite recent advances in understanding the genetic bases of microcephaly, a large number of cases of microcephaly remain unexplained, suggesting that many microcephaly syndromes and associated genes have yet to be identified. Here, we report mutations in PYCR2, which encodes an enzyme in the proline biosynthesis pathway, as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Linkage mapping and whole-exome sequencing identified homozygous mutations (c.355C>T [p.Arg119Cys] and c.751C>T [p.Arg251Cys]) in PYCR2 in the affected individuals of two consanguineous families. A lymphoblastoid cell line from one affected individual showed a strong reduction in the amount of PYCR2. When mutant cDNAs were transfected into HEK293FT cells, both variant proteins retained normal mitochondrial localization but had lower amounts than the wild-type protein, suggesting that the variant proteins were less stable. A PYCR2-deficient HEK293FT cell line generated by genome editing with the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that PYCR2 loss of function led to decreased mitochondrial membrane potential and increased susceptibility to apoptosis under oxidative stress. Morpholino-based knockdown of a zebrafish PYCR2 ortholog, pycr1b, recapitulated the human microcephaly phenotype, which was rescued by wild-type human PYCR2 mRNA, but not by mutant mRNAs, further supporting the pathogenicity of the identified variants. Hypomyelination and the absence of lax, wrinkly skin distinguishes this condition from that caused by previously reported mutations in the gene encoding PYCR2's isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development.
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- 2015
34. Infant mortality: the contribution of genetic disorders
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Wojcik, Monica H., Schwartz, Talia S., Thiele, Katri E., Paterson, Heather, Stadelmaier, Rachel, Mullen, Thomas E., VanNoy, Grace E., Genetti, Casie A., Madden, Jill A., Gubbels, Cynthia S., Yu, Timothy W., Tan, Wen-Hann, and Agrawal, Pankaj B.
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- 2019
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35. Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female
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Rajabi, Farrah, Rodan, Lance H., Jonas, Maureen M., Soul, Janet S., Ullrich, Nicole J., Wessel, Ann, Waisbren, Susan E., Tan, Wen-Hann, Berry, Gerard T., Baumgartner, Matthias, Series Editor, Patterson, Marc, Series Editor, Rahman, Shamima, Series Editor, Peters, Verena, Series Editor, Morava, Eva, Editor-in-Chief, and Zschocke, Johannes, Series Editor
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- 2018
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36. Characterization of the prenatal renal phenotype associated with 17q12, HNF1B, microdeletions.
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Verscaj, Courtney P., Velez‐Bartolomei, Frances, Bodle, Ethan, Chan, Katie, Lyons, Michael J., Thorson, Willa, Tan, Wen‐Hann, Rodig, Nancy, Graham, John M., Peron, Angela, Quintero‐Rivera, Fabiola, Zackai, Elaine H., Thomas, Mary Ann, Stevens, Cathy A., Adam, Margaret P., Bird, Lynne M., Jones, Marilyn C., and Matalon, Dena R.
- Abstract
Objective: Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including congenital abnormalities of the kidney and urinary tract (CAKUT), maturity onset diabetes of the young, type 5, and neurodevelopmental disorders. Structural and/or functional renal disease is the most common phenotypic feature, although the prenatal renal phenotypes and the postnatal correlates have not been well characterized. Method: We reviewed pre‐ and postnatal medical records of 26 cases with prenatally or postnatally identified 17q12/HNF1B microdeletions (by chromosomal microarray or targeted gene sequencing), obtained through a multicenter collaboration. We specifically evaluated 17 of these cases (65%) with reported prenatal renal ultrasound findings. Results: Heterogeneous prenatal renal phenotypes were noted, most commonly renal cysts (41%, n = 7/17) and echogenic kidneys (41%), although nonspecific dysplasia, enlarged kidneys, hydronephrosis, pelvic kidney with hydroureter, and lower urinary tract obstruction were also reported. Postnatally, most individuals developed renal cysts (73%, 11/15 live births), and there were no cases of end‐stage renal disease during childhood or the follow‐up period. Conclusion: Our findings demonstrate that copy number variant analysis to assess for 17q12 microdeletion should be considered for a variety of prenatally detected renal anomalies. It is important to distinguish 17q12 microdeletion from other etiologies of CAKUT as the prognosis for renal function and presence of associated findings are distinct and may influence pregnancy and postnatal management. Key points: What is already known about this topic? Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including renal abnormalities.Cystic renal changes, including cystic dysplasia, are the most commonly reported association postnatally. Hyperechogenic kidneys have been associated prenatally. What does this study add? This study broadens the spectrum of prenatal renal anomalies associated with 17q12 deletions.Despite prenatal onset of renal abnormalities, we demonstrate that individuals with 17q12 deletions displayed no progression to end‐stage renal disease during the postnatal follow‐up period. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Characterization of the prenatal renal phenotype associated with 17q12, HNF1B, microdeletions
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Verscaj, Courtney P., primary, Velez‐Bartolomei, Frances, additional, Bodle, Ethan, additional, Chan, Katie, additional, Lyons, Michael J., additional, Thorson, Willa, additional, Tan, Wen‐Hann, additional, Rodig, Nancy, additional, Graham, John M., additional, Peron, Angela, additional, Quintero‐Rivera, Fabiola, additional, Zackai, Elaine H., additional, Thomas, Mary Ann, additional, Stevens, Cathy A., additional, Adam, Margaret P., additional, Bird, Lynne M., additional, Jones, Marilyn C., additional, and Matalon, Dena R., additional
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- 2023
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38. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development
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Mochida, Ganeshwaran H, Ganesh, Vijay S, de Michelena, Maria I, Dias, Hugo, Atabay, Kutay D, Kathrein, Katie L, Huang, Hsuan-Ting, Hill, R Sean, Felie, Jillian M, Rakiec, Daniel, Gleason, Danielle, Hill, Anthony D, Malik, Athar N, Barry, Brenda J, Partlow, Jennifer N, Tan, Wen-Hann, Glader, Laurie J, Barkovich, A James, Dobyns, William B, Zon, Leonard I, and Walsh, Christopher A
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Biochemistry and Cell Biology ,Biological Sciences ,Regenerative Medicine ,Rare Diseases ,Pediatric ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research - Nonembryonic - Human ,Congenital Structural Anomalies ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,Animals ,Cell Proliferation ,Cerebellar Cortex ,Cyclin-Dependent Kinase Inhibitor p16 ,Endosomal Sorting Complexes Required for Transport ,Gene Expression Regulation ,Developmental ,Genetic Linkage ,HEK293 Cells ,Humans ,Mice ,Microcephaly ,Mitogen-Activated Protein Kinase 7 ,Mutation ,NIH 3T3 Cells ,Neural Stem Cells ,Neurons ,Polymorphism ,Single Nucleotide ,Vesicular Transport Proteins ,Zebrafish ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology ,Genetics - Abstract
Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex but is also suggested to localize to the nuclear matrix and regulate chromatin structure. Here, we show that loss-of-function mutations in human CHMP1A cause reduced cerebellar size (pontocerebellar hypoplasia) and reduced cerebral cortical size (microcephaly). CHMP1A-mutant cells show impaired proliferation, with increased expression of INK4A, a negative regulator of stem cell proliferation. Chromatin immunoprecipitation suggests loss of the normal INK4A repression by BMI in these cells. Morpholino-based knockdown of zebrafish chmp1a resulted in brain defects resembling those seen after bmi1a and bmi1b knockdown, which were partially rescued by INK4A ortholog knockdown, further supporting links between CHMP1A and BMI1-mediated regulation of INK4A. Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells.
- Published
- 2012
39. Deletions of NRXN1 (neurexin‐1) predispose to a wide spectrum of developmental disorders
- Author
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Ching, Michael SL, Shen, Yiping, Tan, Wen‐Hann, Jeste, Shafali S, Morrow, Eric M, Chen, Xiaoli, Mukaddes, Nahit M, Yoo, Seung‐Yun, Hanson, Ellen, Hundley, Rachel, Austin, Christina, Becker, Ronald E, Berry, Gerard T, Driscoll, Katherine, Engle, Elizabeth C, Friedman, Sandra, Gusella, James F, Hisama, Fuki M, Irons, Mira B, Lafiosca, Tina, LeClair, Elaine, Miller, David T, Neessen, Michael, Picker, Jonathan D, Rappaport, Leonard, Rooney, Cynthia M, Sarco, Dean P, Stoler, Joan M, Walsh, Christopher A, Wolff, Robert R, Zhang, Ting, Nasir, Ramzi H, Wu, Bai‐Lin, and Group, on behalf of the Children's Hospital Boston Genotype Phenotype Study
- Subjects
Genetics ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Autism ,Brain Disorders ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Autistic Disorder ,Child ,Child Development Disorders ,Pervasive ,Comparative Genomic Hybridization ,Developmental Disabilities ,Female ,Humans ,Intellectual Disability ,Language Development Disorders ,Male ,Mutation ,Phenotype ,Schizophrenia ,Sequence Deletion ,NRXN1 ,developmental disorders ,array CGH ,NRXN1 exonic deletions ,CNV ,Children's Hospital Boston Genotype Phenotype Study Group ,Clinical Sciences ,Neurosciences - Abstract
Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.
- Published
- 2010
40. Diagnostic utility of array‐based comparative genomic hybridization in a clinical setting
- Author
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Baris, Hagit N, Tan, Wen‐Hann, Kimonis, Virginia E, and Irons, Mira B
- Subjects
Pediatric ,Health Services ,Human Genome ,Biotechnology ,Genetics ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Case-Control Studies ,Child ,Child ,Preschool ,Chromosome Aberrations ,Developmental Disabilities ,Female ,Genome ,Human ,Humans ,Infant ,Infant ,Newborn ,Intellectual Disability ,Male ,Nucleic Acid Hybridization ,Oligonucleotide Array Sequence Analysis ,chromosome aberrations ,chromosome disorders ,gene dosage ,gene duplication ,gene deletion ,microarray comparative genomic hybridization ,copy number variations ,Clinical Sciences - Abstract
Array-based comparative genomic hybridization is a recently introduced technique for the detection of submicroscopic genomic imbalances (deletions or duplications) across the entire genome. To assess the potential utility of a widely available array-based comparative genomic hybridization platform that targets specific, clinically relevant, loci across the genome for cytogenetic diagnosis in a clinical setting, we reviewed the medical records of all 373 patients at Children's Hospital Boston who had normal chromosomal analysis and were tested with this targeted array-based comparative genomic hybridization over a 1-year period from November 1, 2004 to October 31, 2005. These patients were tested because of a suspicion of chromosomal abnormalities based on their clinical presentation. Thirty-six patients (9.7%) had abnormal array-based comparative genomic hybridization results. Twenty patients (5.4%) had potentially pathogenetic genomic imbalances and 16 patients (4.3%) had copy number variations that are not believed to be pathogenetic. Thirteen of 234 patients (5.6%) with mental retardation/global developmental delay, 10/114 patients (8.8%) with facial dysmorphism, 5/58 patients (8.6%) with multiple congenital anomalies, and 4/35 patients (11.4%) with both facial dysmorphism and multiple congenital anomalies had potentially pathogenetic genomic imbalances. Targeted array-based comparative genomic hybridization is a clinically available test that is useful in the evaluation of patients suspected of having chromosomal disorders. However, it is best used as an adjunct to chromosomal analysis when a clear genetic diagnosis is unavailable.
- Published
- 2007
41. P192: Deep neurologic phenotyping and biomarker development in Bohring-Opitz syndrome using EEGs, neurodevelopmental assessments, and DNA methylation signature
- Author
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Russell, Bianca, Sloan, Julia, Nariai, Hiroki, Ludwig, Natasha, Dickinson, Abigail, Awamleh, Zain, Weksberg, Rosanna, Lin, Isabella, Arboleda, Valerie, and Tan, Wen-Hann
- Published
- 2024
- Full Text
- View/download PDF
42. Microcephaly and chorioretinopathy associated with TUBGCP4: a case report and a review of the literature.
- Author
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Yahalom, Claudia, Woods, Russell L, Akula, James D, Tan, Wen-Hann, and Fulton, Anne
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LITERATURE reviews ,MICROCEPHALY ,VISION disorders ,TETRALOGY of Fallot ,DEVELOPMENTAL delay ,LOW vision - Abstract
Microcephaly and chorioretinopathy (MCCRP) is a rare autosomal recessive (AR) disorder characterized by microcephaly, developmental delay, chorioretinopathy, and visual impairment. We characterized the long-term phenotype of an additional patient with MCCRP associated with TUBCGP4 pathogenic variants and analysed previously reported cases in the literature. Analysis of clinical and genetic data of a patient with TUBGCP4-related MCCRP followed for more than 19 years and literature search for previously reported patients with TUBCGP4 variants using PubMed, Scopus, and Google Scholar. Molecular diagnosis using exome sequencing demonstrated two TUBCGP4 variants in trans: c.1669C>T (p.Arg557*) and c.1746 G>T (p.Leu582=). Clinical characteristics included microcephaly, microphthalmia, punched-out chorioretinal lesions, vision impairment, nystagmus, Tetralogy of Fallot and neurodevelopmental delay. Another six previously reported cases of TUBCGP4-related MCCRP were identified. Their clinical and genetic characteristics are compared. TUBCGP4-related microcephaly and chorioretinopathy, is a rare autosomal recessive neuro-ophthalmic disorder. Clinical characteristics in our proband have remained stable for two decades. The pathophysiology of this syndrome is not yet fully understood. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
43. Identification of a novel polymorphism—the duplication of the NPHP1 (nephronophthisis 1) gene
- Author
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Baris, Hagit, Bejjani, Bassem A, Tan, Wen‐Hann, Coulter, David L, Martin, Judith A, Storm, Andrea L, Burton, Barbara K, Saitta, Sulagna C, Gajecka, Marzena, Ballif, Blake C, Irons, Mira B, Shaffer, Lisa G, and Kimonis, Virginia E
- Subjects
Adaptor Proteins ,Signal Transducing ,Child ,Child ,Preschool ,Chromosomes ,Human ,Pair 2 ,Cytoskeletal Proteins ,Developmental Disabilities ,Female ,Gene Duplication ,Humans ,In Situ Hybridization ,Fluorescence ,Infant ,Male ,Membrane Proteins ,Polymorphism ,Genetic ,Proteins ,Speech Disorders ,Genetics ,Clinical Sciences - Published
- 2006
44. Hypothelia, syndactyly, and ear malformation—A variant of the scalp–ear–nipple syndrome?: Case report and review of the literature (Am J Med Genet 134A: 220–222 (2005))
- Author
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Baris, Hagit, Tan, Wen‐Hann, and Kimonis, Virginia E
- Subjects
Genetics ,Clinical Sciences - Published
- 2005
45. Cockayne syndrome: The developing phenotype
- Author
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Tan, Wen‐Hann, Baris, Hagit, Robson, Caroline D, and Kimonis, Virginia E
- Subjects
Congenital Structural Anomalies ,Brain Disorders ,Neurosciences ,Rare Diseases ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,Clinical Research ,Dental/Oral and Craniofacial Disease ,Adult ,Age of Onset ,Cockayne Syndrome ,Disease Progression ,Fatal Outcome ,Female ,Globus Pallidus ,Humans ,Tomography ,X-Ray Computed ,Cockayne syndrome ,microcephaly ,neurodevelopmental regression ,basal ganglia calcification ,Genetics ,Clinical Sciences - Abstract
Cockayne syndrome is a rare autosomal recessive condition comprising microcephaly, "cachectic dwarfism" and progressive neurological degeneration. We present a 21-year-old woman who was not diagnosed with Cockayne syndrome type I until she was 21 years old. Family photographs demonstrated that the phenotype of Cockayne syndrome did not become evident until she was 8 years old. She had severe microcephaly, micrognathia, protruding ears, dental overcrowding with caries, progressive spastic quadriparesis, and severe developmental regression. Her head computed tomography (CT) showed bilateral calcification of the globus pallidus and global atrophy. The purpose of this clinical report is to alert clinicians to the fact that the phenotypic features of Cockayne syndrome may be very subtle early in the course of the disease.
- Published
- 2005
46. Clinical findings in 39 individuals with Bohring–Opitz syndrome from a global patient‐driven registry with implications for tumor surveillance and recurrence risk
- Author
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Russell, Bianca E., primary, Kianmahd, Rebecca R., additional, Munster, Chelsea, additional, Yu, Anna, additional, Ahad, Leena, additional, and Tan, Wen‐Hann, additional
- Published
- 2023
- Full Text
- View/download PDF
47. AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia
- Author
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CMM Groep Maurice, Cancer, DT Schildpad, Integrale & Alg. Kindergen Patientenzorg, Other research (not in main researchprogram), Pathologie Pathologen staf, Regenerative Medicine and Stem Cells, Terhal, Paulien, Venhuizen, Anton J, Lessel, Davor, Tan, Wen-Hann, Alswaid, Abdulrahman, Grün, Regina, Alzaidan, Hamad I, von Kroge, Simon, Ragab, Nada, Hempel, Maja, Kubisch, Christian, Novais, Eduardo, Cristobal, Alba, Tripolszki, Kornelia, Bauer, Peter, Fischer-Zirnsak, Björn, Nievelstein, Rutger A J, van Dijk, Atty, Nikkels, Peter, Oheim, Ralf, Hahn, Heidi, Bertoli-Avella, Aida, Maurice, Madelon M, Kornak, Uwe, CMM Groep Maurice, Cancer, DT Schildpad, Integrale & Alg. Kindergen Patientenzorg, Other research (not in main researchprogram), Pathologie Pathologen staf, Regenerative Medicine and Stem Cells, Terhal, Paulien, Venhuizen, Anton J, Lessel, Davor, Tan, Wen-Hann, Alswaid, Abdulrahman, Grün, Regina, Alzaidan, Hamad I, von Kroge, Simon, Ragab, Nada, Hempel, Maja, Kubisch, Christian, Novais, Eduardo, Cristobal, Alba, Tripolszki, Kornelia, Bauer, Peter, Fischer-Zirnsak, Björn, Nievelstein, Rutger A J, van Dijk, Atty, Nikkels, Peter, Oheim, Ralf, Hahn, Heidi, Bertoli-Avella, Aida, Maurice, Madelon M, and Kornak, Uwe
- Published
- 2023
48. Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS)
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Tjeertes, Jorrit, primary, Bacino, Carlos A., additional, Bichell, Terry Jo, additional, Bird, Lynne M., additional, Bustamante, Mariana, additional, Crean, Rebecca, additional, Jeste, Shafali, additional, Komorowski, Robert W., additional, Krishnan, Michelle L., additional, Miller, Meghan T., additional, Nobbs, David, additional, Ochoa-Lubinoff, Cesar, additional, Parkerson, Kimberly A., additional, Rotenberg, Alexander, additional, Sadhwani, Anjali, additional, Shen, Mark D., additional, Squassante, Lisa, additional, Tan, Wen-Hann, additional, Vincenzi, Brenda, additional, Wheeler, Anne C., additional, Hipp, Joerg F., additional, and Berry-Kravis, Elizabeth, additional
- Published
- 2023
- Full Text
- View/download PDF
49. O20: The natural history of Angelman syndrome: Sixteen years and 450 individuals later…*
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Tan, Wen-Hann, primary, Anderson, Katherine, additional, Sadhwani, Anjali, additional, Billie Au, Ping Yee, additional, Bacino, Carlos, additional, Berry-Kravis, Elizabeth, additional, Boelman, Cyrus, additional, Carson, Robert, additional, DeRamus, Margaret, additional, Duis, Jessica, additional, Murias, Kara, additional, Ochoa-Lubinoff, Cesar, additional, Peters, Sarika, additional, Sell, Erick, additional, Skinner, Steven, additional, Talboy, Amy, additional, Wheeler, Anne, additional, Wink, Logan, additional, Gwaltney, Angela, additional, and Bird, Lynne, additional
- Published
- 2023
- Full Text
- View/download PDF
50. O43: Characterization of the prenatal renal phenotype associated with 17q12/HNF1B microdeletions
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Verscaj, Courtney, primary, Velez-Bartolomei, Frances, additional, Bodle, Ethan, additional, Chan, Katie, additional, Lyons, Michael, additional, Thorson, Willa, additional, Tan, Wen-Hann, additional, Graham, John, additional, Peron, Angela, additional, Quintero-Rivera, Fabiola, additional, Zackai, Elaine, additional, Thomas, Mary Ann, additional, Stevens, Cathy, additional, Adam, Margaret, additional, Bird, Lynne, additional, Jones, Marilyn, additional, and Matalon, Dena, additional
- Published
- 2023
- Full Text
- View/download PDF
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