11 results on '"Chansonette Badduke"'
Search Results
2. Comprehensive characterization of a Canadian cohort of von Hippel‐Lindau disease patients
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Shereen Ezzat, Wei Xu, Normand Laperriere, Saleh Albanyan, Garrett Bullivant, Zsuzanna Lichner, Payal Jani, Andreea Chiorean, Gelareh Zadeh, Rachel H. Giles, Fady Hannah-Shmouni, Marta Szybowska, Lior Krimus, Marisa Sit, Yasser Salama, Yuvreet Kaur, Chansonette Badduke, Nathan F. Schachter, Michael A.S. Jewett, Raymond H. Kim, Hatem Krema, David Malkin, Tracy Stockley, Ozgur Mete, Karen Gomez Hernandez, Sylvia L. Asa, Cara Inglese, Harriet Druker, Bailey Gallinger, and Jonathan D. Wasserman
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Adult ,Central Nervous System ,Male ,0301 basic medicine ,Oncology ,Canada ,medicine.medical_specialty ,von Hippel-Lindau Disease ,Retinal Neoplasm ,Adolescent ,endocrine system diseases ,Mutation, Missense ,Penetrance ,Pheochromocytoma ,Disease ,030105 genetics & heredity ,urologic and male genital diseases ,Frameshift mutation ,Young Adult ,03 medical and health sciences ,Hemangioblastoma ,Internal medicine ,Genetics ,medicine ,Humans ,Missense mutation ,Von Hippel–Lindau disease ,Child ,neoplasms ,Genetics (clinical) ,Aged ,Aged, 80 and over ,business.industry ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Pedigree ,030104 developmental biology ,Von Hippel-Lindau Tumor Suppressor Protein ,Child, Preschool ,Female ,business - Abstract
Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or β-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL.
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- 2019
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3. Exome sequencing identified a de novo mutation of PURA gene in a patient with familial Xp22.31 microduplication
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Laura Arbour, Suzanne M E Lewis, Sally Martell, Mary B. Connolly, Hani Bagheri, Ying Qiao, Wendy P. Robinson, Flamingo Tang, Evica Rajcan-Separovic, and Chansonette Badduke
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Male ,0301 basic medicine ,Proband ,Heterozygote ,Developmental Disabilities ,Mutation, Missense ,030105 genetics & heredity ,Biology ,DNA sequencing ,Craniofacial Abnormalities ,03 medical and health sciences ,Chromosome Duplication ,Gene duplication ,Genetics ,medicine ,Humans ,Missense mutation ,Child ,Gene ,Genetics (clinical) ,X chromosome ,Exome sequencing ,Chromosomes, Human, X ,Genetic Diseases, X-Linked ,Syndrome ,General Medicine ,Hypotonia ,DNA-Binding Proteins ,Phenotype ,030104 developmental biology ,medicine.symptom ,Transcription Factors - Abstract
The clinical significance of Xp22.31 microduplication is controversial as it is reported in subjects with developmental delay (DD), their unaffected relatives and unrelated controls. We performed multifaceted studies in a family of a boy with hypotonia, dysmorphic features and DD who carried a 600 Kb Xp22.31 microduplication (7515787-8123310bp, hg19) containing two genes, VCX and PNPLA4. The duplication was transmitted from his cognitively normal maternal grandfather. We found no evidence of the duplication causing the proband's DD and congenital anomalies based on unaltered expression of PNPLA4 in the proband and his mother in comparison to controls and preferential activation of the paternal chromosome X with Xp22.31 duplication in proband's mother. However, a de novo, previously reported deleterious, missense mutation in Pur-alpha gene (PURA) (5q31.2), with a role in neuronal differentiation was detected in the proband by exome sequencing. We propose that the variability in the phenotype in carriers of Xp22.31 microduplication can be due to a second and more deleterious genetic mutation in more severely affected carriers. Widespread use of whole genome next generation sequencing in families with Xp22.31 CNV could help identify such cases.
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- 2019
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4. eP128: A novel CSNK1E variant in a patient with autism spectrum disorder
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Ria Garg, Chansonette Badduke, and Anne Slavotinek
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Genetics (clinical) - Published
- 2022
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5. 47. Tumour-only NGS profiling: Application of data filters to identify candidate germline variants
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Nicole Park, Chansonette Badduke, Brittany Gillies, Geoffrey Watson, Tong Zhang, Raymond H. Kim, Philippe L. Bedard, and Tracy Stockley
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Cancer Research ,Genetics ,Molecular Biology - Published
- 2022
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6. 45. Community curation for Von Hippel Lindau disease
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Samantha Macpherson, Safa Ansar, Kirsten Farncombe, Veronica Andric, Chansonette Badduke, Andreea Chiorean, Sean Delong, Yizhuo Gao, Deborah Ritter, Courtney Thaxton, and Raymond Kim
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Cancer Research ,Genetics ,Molecular Biology - Published
- 2022
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7. Whole exome sequencing of families with 1q21.1 microdeletion or microduplication
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Suzanne M E Lewis, Sally Martell, Chansonette Badduke, Wendy P. Robinson, Evica Rajcan-Separovic, Flamingo Tang, David Cowieson, Maria S. Peñaherrera, Allen Volchuk, and Ying Qiao
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0301 basic medicine ,Proband ,Genetics ,In silico ,Biology ,Phenotype ,DNA sequencing ,X-inactivation ,03 medical and health sciences ,030104 developmental biology ,Gene duplication ,Gene ,Genetics (clinical) ,Exome sequencing - Abstract
Recurrent microduplications/microdeletions of 1q21.1 are characterized by variable phenotypes ranging from normal development to developmental delay (DD) and congenital anomalies. Their interpretation is challenging especially in families with affected and unaffected carriers. We used whole exome sequencing (WES) to look for sequence variants in two male probands with inherited 1q21.1 CNVs that could explain their more severe phenotypes. One proband had a 1q21.1 deletion transmitted from maternal grandmother, while the other had a paternal duplication. We found mutations in five genes (SMPD1, WNK3, NOS1, ATF6, and EFHC1) that could contribute to the more severe phenotype in the probands in comparison to their mildly affected or unaffected 1q21.1 CNV carrying relatives. Interestingly, all genes have roles in stress responses (oxidative/Endoplasmic Reticulum (ER)/osmotic). One of the variants was in an X-linked gene WNK3 and segregated with the developmental features and X inactivation pattern in the family with 1q21.1 deletion transmitted from maternal grandmother. In silico analysis of all rare deleterious variants in both probands identified enrichment in nervous system diseases, metabolic pathways, protein processing in the ER and protein export. Our studies suggest that rare deleterious variants outside of the 1q21.1 CNV, individually or as a pool, could contribute to phenotypic variability in carriers of this CNV. Rare deleterious variants in stress response genes are of interest and raise the possibility of susceptibility of carriers to variable environmental influences. Next generation sequencing of additional familial cases with 1q21.1 CNV could further help determine the possible causes of phenotypic variability in carriers of this CNV.
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- 2017
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8. Author response for 'Comprehensive Characterization of a Canadian Cohort of von Hippel‐Lindau Disease Patients'
- Author
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Normand Laperriere, Sylvia L. Asa, Andreea Chiorean, Michael A.S. Jewett, Fady Hannah-Shmouni, Karen Gomez Hernandez, Harriet Druker, Bailey Gallinger, Yuvreet Kaur, Saleh Albanyan, Yasser Salama, David Malkin, Tracy Stockley, Payal Jani, Ozgur Mete, Shereen Ezzat, Gelareh Zadeh, Cara Inglese, Raymond H. Kim, Wei Xu, Hatem Krema, Jonathan Wasserman, Garrett Bullivant, Rachel H. Giles, Marta Szybowska, Lior Krimus, Marisa Sit, Zsuzanna Lichner, Chansonette Badduke, and Nathan F. Schachter
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Cohort ,medicine ,Von Hippel–Lindau disease ,medicine.disease ,business - Published
- 2019
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9. Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis
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Mark O'Driscoll, Anna Lehman, Xianghong Shan, Bruno Maranda, Cheryl Y. Gregory-Evans, Małgorzata J.M. Nowaczyk, Ying Qiao, Chansonette Badduke, Rita Colnaghi, Jiadi Wen, Robert S. Wildin, Jennifer Eichmeyer, Iga Abramowicz, Diana Alcantara, Christopher Dunham, Suzanne M E Lewis, Sally Martell, Hani Bagheri, and Evica Rajcan-Separovic
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0301 basic medicine ,Male ,Candidate gene ,Microcephaly ,Adolescent ,Developmental Disabilities ,Receptors, Cytoplasmic and Nuclear ,lcsh:Medicine ,Chromosome Disorders ,Biology ,Karyopherins ,03 medical and health sciences ,medicine ,Genetics ,Animals ,Humans ,Abnormalities, Multiple ,Child ,Zebrafish ,Gene knockdown ,lcsh:R ,Infant ,Nuclear Proteins ,General Medicine ,Microdeletion syndrome ,biology.organism_classification ,medicine.disease ,Phenotype ,2p15p16.1 microdeletion syndrome ,Hypotonia ,Proto-Oncogene Proteins c-rel ,Repressor Proteins ,030104 developmental biology ,Child, Preschool ,Chromosomes, Human, Pair 2 ,Gene Knockdown Techniques ,Female ,medicine.symptom ,Chromosome Deletion ,Carrier Proteins ,Research Article - Abstract
The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34, BCL11A, and REL) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients’ lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients’ LCLs. Other pathways associated with these genes (e.g., NF-κB and Wnt signaling as well as the DNA damage response) were not impaired in patients’ LCLs. Knockdown of xpo1a, rel, bcl11aa, and bcl11ab resulted in abnormal zebrafish embryonic development including microcephaly, dysmorphic body, hindered growth, and small fins as well as structural brain abnormalities. Our multifaceted analysis strongly implicates XPO1, REL, and BCL11A as candidate genes for 2p15p16.1 microdeletion syndrome.
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- 2016
10. MG-118 Towards understanding phenotypic variability using exome sequencing
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Allen Volchuk, Flamingo Tang, Sally Martell, Chansonette Badduke, Sandra L. Marles, Eva W.C. Chow, Suzanne M E Lewis, David Cowieson, Ying Qiao, and Evica Rajcan-Separovic
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Proband ,Genetics ,Mutation ,Biology ,medicine.disease_cause ,Compound heterozygosity ,Genome ,Phenotype ,Frameshift mutation ,medicine ,Gene ,Genetics (clinical) ,Exome sequencing - Abstract
Background The recurrent 1q21.1 CNV has been associated with considerable phenotypic variability ranging from normal to severe neurodevelopmental delay, noted even among members of the same family. The reason for this variability is unknown. Objective We screened for mutations within the 1q21.1 CNV or genome wide that could explain the phenotypic variability among ten 1q21.1 carriers from 4 families. Methods Whole exome sequencing (WES) was performed on 6 subjects with deletions, 4 subjects with duplications and their 4 unaffected family members using an Illumina HiSeq 2000 sequencing platform. Golden Helix SVS v8.1.5 was used for raw data analysis. We assessed deleterious (e.g. splicing, frameshift, stop gain or loss) de novo , recessive or compound heterozygous mutation in the most severely affected probands from three families, as well as rare and pathogenic mutations inherited from their 1q21.1 carrier parents. Eight bioinformatics tools were used to assess functional damage and conservation of variants. Their expression pattern and role in disease based on literature review were also considered. Results We found no pathogenic mutations in the 1q21.1 CNV region in any of the subjects. One homozygous mutation and six pathogenic mutations inherited from the affected parent were selected for follow-up and involved genes MADD, ASIC3, ATF6, NOS1, PIK3C2G and ROMO1 and NAV2. It is of interest that the majority of these genes have a role in stress response to a variety of environmental conditions such (e.g. pH, oxygen levels) or in endoplasmatic reticulum stress response. Conclusions Impaired stress response, due to pathogenic mutations, in carriers of 1q21.1 CNVs combined with more or less favourable environmental conditions during early development could contribute to their phenotypic variability and severity.
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- 2015
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11. miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability
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Evica Rajcan-Separovic, Suzanne M E Lewis, Paul Pavlidis, Chansonette Badduke, Ying Qiao, and Eloi Mercier
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Male ,Proband ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Copy Number Variations ,endocrine system diseases ,Micro RNA (miRNA) ,Copy number variants (CNVs) ,Copy number variant regions (CNVRs) ,Genomics ,Biology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Intellectual Disability ,Databases, Genetic ,microRNA ,mental disorders ,Genetics ,Humans ,Gene silencing ,Copy-number variation ,Functional pathways ,Gene ,030304 developmental biology ,0303 health sciences ,Case-control study ,MicroRNAs ,Intellectual disabilities (ID) ,Case-Control Studies ,Female ,DNA microarray ,030217 neurology & neurosurgery ,Research Article ,Biotechnology - Abstract
Background MicroRNAs (miRNAs) are a family of short, non-coding RNAs modulating expression of human protein coding genes (miRNA target genes). Their dysfunction is associated with many human diseases, including neurodevelopmental disorders. It has been recently shown that genomic copy number variations (CNVs) can cause aberrant expression of integral miRNAs and their target genes, and contribute to intellectual disability (ID). Results To better understand the CNV-miRNA relationship in ID, we investigated the prevalence and function of miRNAs and miRNA target genes in five groups of CNVs. Three groups of CNVs were from 213 probands with ID (24 de novo CNVs, 46 familial and 216 common CNVs), one group of CNVs was from a cohort of 32 cognitively normal subjects (67 CNVs) and one group of CNVs represented 40 ID related syndromic regions listed in DECIPHER (30 CNVs) which served as positive controls for CNVs causing or predisposing to ID. Our results show that 1). The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P de novo CNV groups compared to common CNV groups. 3). More miRNA target genes are found in de novo, familial and DECIPHER CNVs than in the common CNV subgroup (P de novo and DECIPHER CNV subgroups. Conclusions Our findings reveal an increase in miRNA and miRNA target gene content in de novo versus common CNVs in subjects with ID. Their expression profile and participation in pathways support a possible role of miRNA copy number change in cognition and/or CNV-mediated developmental delay. Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.
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