20 results on '"VPS13B gene"'
Search Results
2. Deletion as novel variants in VPS13B gene in Cohen syndrome: Case series
- Author
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Kang Li, Ma Yixuan, and Zhao Peng
- Subjects
cohen syndrome ,mutation ,vps13b gene ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Cohen syndrome (OMIM No. # 216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. Clinical manifestations include hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, and neutropenia. To date, more than 200 mutations of VPS13B have been reported in over 1,000 Cohen syndrome patients. This article reviews the clinical data of two cases of Cohen syndrome diagnosed by whole exome sequencing.
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- 2023
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- View/download PDF
3. Cohen syndrome in two patients from China.
- Author
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Gong, Jiaoe, Zhang, Lily, Long, Yanwei, Xiao, Bo, and Long, Hongyu
- Subjects
- *
GENETIC variation , *GENETIC testing , *INTELLECTUAL disabilities , *SYNDROMES , *DEVELOPMENTAL delay , *FRAGILE X syndrome - Abstract
Background: Cohen syndrome (CS; OMIM 216550) is a rare syndrome with evident clinical heterogeneity. The diverse phenotype comprises early‐onset hypotonia and developmental delays, intellectual disabilities, microcephaly, hypermobile joints, neutropenia, myopia, and characteristic facial features. The disease is rarely reported. Vacuolar Protein Sorting 13 Homolog B (VPS13B; OMIM 607817) is the only causative gene of CS. Methods: Blood samples sourced from both siblings and parents were sent to identify mutations by trio‐WES, and changes in the patient's condition were understood through consultation data and follow‐up. Results: We reported two siblings affected by developmental delay, microcephaly, intellectual disability, and facial features. The siblings' WES detected compound heterozygous variants in the exon region of VPS13B (NM_017890): c.9337A>T and c.8551A>C. Conclusion: Two individuals were diagnosed with CS by genetic testing and clinical features. In addition, we conduct a brief review of the reports on the Chinese population with CS and reinforce the understanding of the correlation between genotype–phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Identification of a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing
- Author
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Hu X, Huang T, Liu Y, Zhang L, Zhu L, Peng X, and Zhang S
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cohen syndrome ,vps13b gene ,heterozygous mutation ,heterozygous deletion ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Xiaoyun Hu, Tao Huang, Yun Liu, Lina Zhang, Li Zhu, Xiaohong Peng, Sufang Zhang Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Tao Huang Tel +86 13970012590Email huangtao99@email.cnObjective: The present study aims to investigate the clinical features and diagnostic characteristics of children with Cohen syndrome caused by the vacuolar protein sorting 13 homolog B (VPS13B) gene mutation and to review the relevant literature to provide a reference for genetic counseling and the diagnosis of Cohen syndrome.Methods: The clinical data and molecular genetic test results of a child with Cohen syndrome were retrospectively analyzed and a review of the relevant literature was conducted.Results: A two-year-and-four-month-old boy was referred to the hospital for recurrent fever and shortness of breath. On physical examination, the boy was found to have growth retardation, thick bushy hair, microcephaly, hypertelorism, down-slanting palpebral fissures, and hypotonia. Genetic testing was performed, and the results suggested the presence of exon 20– 32 heterozygous deletion and c.8275 delC (p.R2759 fs*18) heterozygous variant on the VPS13B gene from phenotypically normal parents. These two mutation loci have not been reported in the literature, and they were predicted by relevant software to be pathogenic variants.Conclusion: We identified two novel variants in the VPS13B gene (exon 20– 32 heterozygous deletion and c.8275 delC heterozygous variant) in a boy with Cohen syndrome, thus extending the spectrum of VPS13B gene variants in patients with Cohen syndrome.Keywords: Cohen syndrome, VPS13B gene, heterozygous mutation, heterozygous deletion
- Published
- 2021
5. Cohen syndrome in two patients from China
- Author
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Jiaoe Gong, Lily Zhang, Yanwei Long, Bo Xiao, and Hongyu Long
- Subjects
Chinese ,Cohen syndrome ,compound heterozygous mutation ,VPS13B gene ,Genetics ,QH426-470 - Abstract
Abstract Background Cohen syndrome (CS; OMIM 216550) is a rare syndrome with evident clinical heterogeneity. The diverse phenotype comprises early‐onset hypotonia and developmental delays, intellectual disabilities, microcephaly, hypermobile joints, neutropenia, myopia, and characteristic facial features. The disease is rarely reported. Vacuolar Protein Sorting 13 Homolog B (VPS13B; OMIM 607817) is the only causative gene of CS. Methods Blood samples sourced from both siblings and parents were sent to identify mutations by trio‐WES, and changes in the patient's condition were understood through consultation data and follow‐up. Results We reported two siblings affected by developmental delay, microcephaly, intellectual disability, and facial features. The siblings' WES detected compound heterozygous variants in the exon region of VPS13B (NM_017890): c.9337A>T and c.8551A>C. Conclusion Two individuals were diagnosed with CS by genetic testing and clinical features. In addition, we conduct a brief review of the reports on the Chinese population with CS and reinforce the understanding of the correlation between genotype–phenotype.
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- 2022
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6. Cohen Syndrome With Complex Medical Complications: A Case Report.
- Author
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Milhem FS, Awashra A, Hamshary H, Sawaftah Z, Khaled A, Nabresi N, and Salman I
- Abstract
Cohen syndrome (CS) is a rare autosomal recessive disorder marked by developmental delays, distinct facial features, and a variety of systemic manifestations. We present a case of a 28-year-old male previously misdiagnosed with Prader-Willi syndrome who exhibited recurrent generalized weakness, fever, fatigue, and significant hemoglobin drops requiring multiple blood transfusions due to thalassemia major. The patient displayed characteristic CS features, including developmental delays, distinct facial characteristics, morbid obesity, and heterochromia iridis. Severe gastrointestinal bleeding led to a diagnosis of ulcerative colitis (UC) via colonoscopy. Management included blood transfusions, hydrocortisone, mesalamine, and azathioprine, resulting in stabilized UC and improved overall health. CS presents with a spectrum of clinical features that overlap with other syndromic conditions, necessitating careful differential diagnosis. Early diagnosis and supportive care significantly improve quality of life and help manage complications effectively., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Milhem et al.)
- Published
- 2024
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7. Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms
- Author
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Sha Zhao, Zhenqing Luo, Zhenghui Xiao, Liping Li, Rui Zhao, Yongjia Yang, and Yan Zhong
- Subjects
Cohen syndrome ,Hyperlinear palm ,VPS13B gene ,Mutation ,Chinese ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.
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- 2019
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8. Cohen syndrome coincident with epidermolytic palmoplantar keratoderma caused by novel KRT9 gene mutation: A rare case report.
- Author
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Shu, Yanping, Hou, Yongzhe, and Zhang, Qin
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- 2023
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9. Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome.
- Author
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Lou, Guiyu, Ke, Yang, Zhang, Yuwei, Liangjie, Guo, Shama, Samaa Abdelmonem, Qi, Na, Qin, Litao, Liao, Shixiu, and Zhao, Yuanyin
- Abstract
Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. In the current study, a Chinese family has two young sibling cases having a developmental delay, physical obesity, high myopia, and a special face, which suspected to be CS. The purpose of the study was to identify variants and further analyze their pathogenicity for CS. Next-generation sequencing (NGS) revealed a compound heterozygous mutation in VPS13B gene in the proband, which comprises a frameshift mutation in NM_017890.4: c.10076_10077delCA (p.T3359fs*29) and a putative splice site mutation in c.6940 + 1G > T. Both Minigene assay in vitro and splicing assay in vivo confirmed that the splicing mutation in c.6940 + 1G > T generates a frameshift transcript with whole exon 38 skipping. Eventually, quantitative real-time PCR demonstrated that either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level. Functional studies of variants identified in CS patients are essential for their subsequent genetic counseling and prenatal diagnoses and could also be the start point for new therapeutic approaches, currently based only on symptomatic treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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10. Pseudohypoaldosteronism Type 1B and Cohen Syndrome: Novel Mutation, Unusual Combination, and Presentation.
- Author
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Alsaleh Y, Al Ghadeer HA, Aljabri A, Alhashim Z, Mohamed M, Busaleh F, Alramadhan FA, and Alghazal MM
- Abstract
Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disorder of resistance to aldosterone and presents with hyponatremia, hyperkalemia, and metabolic acidosis. Cohen syndrome (CS) is another rare inherited disease. Concurrent presentation with pseudohypoaldosteronism makes it so extraordinary and implies more challenges for clinicians. We report a case of a female with Cohen syndrome (novel mutation) and systemic pseudohypoaldosteronism, as well as the challenges we have encountered in the management of this patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alsaleh et al.)
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- 2024
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11. A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome.
- Author
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Koehler, Katrin, Schuelke, Markus, Hell, Anna K., Schittkowski, Michael, Huebner, Angela, and Brockmann, Knut
- Abstract
Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19‐year‐old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole‐genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations
- Author
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Imen Rejeb, Houweyda Jilani, Yasmina Elaribi, Syrine Hizem, Lamia Hila, Julia Lauer Zillahrdt, Jamel Chelly, and Lamia Benjemaa
- Subjects
Cohen syndrome ,VPS13B gene ,Compound heterozygous mutation ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Cohen syndrome is a rare autosomal recessive developmental disorder that comprises variable clinical features counting developmental delay, pigmentary retinopathy, myopia, acquired microcephaly, truncal obesity, joint hypermobility, friendly disposition and intermittent neutropenia. VPS13B (vacuolar protein sorting 13, yeast, homologue of B) gene is the only gene responsible for Cohen Syndrome, causative mutations include nonsense, missense, indel and splice-site variants. The integrity of the Golgi apparatus requires the presence of the peripheral membrane protein VPS13B that have an essential function in intracellular protein transport and vesicle-mediated sorting. Case presentation In this study, we performed whole exome sequencing (WES) in a Tunisian family with two young cases having developmental delay, hypotonia, autism spectrum disorder, ptosis and thick hair and eyebrows. The proposita presented also pigmentory retinopathy. Compound heterozygous mutation in VPS13B gene was detected by WES. This mutation inherited from healthy heterozygous parents, supports an unpredictable clinical diagnosis of Cohen Syndrome. The proband’s phenotype is explained by the presence of compound heterozygous mutations in the VPS13B gene. This finding refined the understanding of genotype-phenotype correlation. Conclusions This is the first report of a Tunisian family with Cohen syndrome mutated in the VPS13B gene.
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- 2017
- Full Text
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13. 幼儿精神运动发育落后伴中性粒细胞减少1 年余.
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张凡, 石秀玉, 刘丽英, 刘雨田, and 邹丽萍
- Subjects
SHOULDER ,HIP joint ,MUSCLE hypotonia ,FACIES ,INFANTS - Abstract
Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2018
14. First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations.
- Author
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Rejeb, Imen, Jilani, Houweyda, Elaribi, Yasmina, Hizem, Syrine, Hila, Lamia, Zillahrdt, Julia Lauer, Chelly, Jamel, and Benjemaa, Lamia
- Subjects
- *
GENETIC disorders , *NEUTROPENIA , *MICROCEPHALY , *GOLGI apparatus , *AUTISM spectrum disorders - Abstract
Background: Cohen syndrome is a rare autosomal recessive developmental disorder that comprises variable clinical features counting developmental delay, pigmentary retinopathy, myopia, acquired microcephaly, truncal obesity, joint hypermobility, friendly disposition and intermittent neutropenia. VPS13B (vacuolar protein sorting 13, yeast, homologue of B) gene is the only gene responsible for Cohen Syndrome, causative mutations include nonsense, missense, indel and splice-site variants. The integrity of the Golgi apparatus requires the presence of the peripheral membrane protein VPS13B that have an essential function in intracellular protein transport and vesicle-mediated sorting. Case presentation: In this study, we performed whole exome sequencing (WES) in a Tunisian family with two young cases having developmental delay, hypotonia, autism spectrum disorder, ptosis and thick hair and eyebrows. The proposita presented also pigmentory retinopathy. Compound heterozygous mutation in VPS13B gene was detected by WES. This mutation inherited from healthy heterozygous parents, supports an unpredictable clinical diagnosis of Cohen Syndrome. The proband's phenotype is explained by the presence of compound heterozygous mutations in the VPS13B gene. This finding refined the understanding of genotype-phenotype correlation. Conclusions: This is the first report of a Tunisian family with Cohen syndrome mutated in the VPS13B gene. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
15. Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms
- Author
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Zhao, Sha, Luo, Zhenqing, Xiao, Zhenghui, Li, Liping, Zhao, Rui, Yang, Yongjia, and Zhong, Yan
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- 2019
- Full Text
- View/download PDF
16. Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms
- Author
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Zhenqing Luo, Zhenghui Xiao, Yongjia Yang, Sha Zhao, Rui Zhao, Liping Li, and Yan Zhong
- Subjects
Male ,0301 basic medicine ,lcsh:Internal medicine ,China ,Microcephaly ,lcsh:QH426-470 ,Developmental Disabilities ,Nonsense mutation ,Vesicular Transport Proteins ,Case Report ,Biology ,Compound heterozygosity ,medicine.disease_cause ,Fingers ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Intellectual Disability ,Myopia ,Genetics ,medicine ,Humans ,Genetic Testing ,Obesity ,lcsh:RC31-1245 ,Child ,Genetics (clinical) ,Exome sequencing ,Cohen syndrome ,Mutation ,Chinese ,Retinal Degeneration ,Hand ,medicine.disease ,Pedigree ,VPS13B ,lcsh:Genetics ,Phenotype ,030104 developmental biology ,Child, Preschool ,Hyperlinear palm ,Muscle Hypotonia ,Female ,VPS13B gene ,030217 neurology & neurosurgery - Abstract
Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.
- Published
- 2019
17. A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome
- Author
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M. P. Schittkowski, Angela Huebner, Katrin Koehler, Anna K. Hell, Knut Brockmann, and Markus Schuelke
- Subjects
0301 basic medicine ,Adult ,Male ,Microcephaly ,VPS13B gene ,Cohen syndrome ,prepubertal alacrima ,prepubertal anhidrosis ,Developmental Disabilities ,Nonsense mutation ,Vesicular Transport Proteins ,030105 genetics & heredity ,Alacrima ,Short stature ,Fingers ,03 medical and health sciences ,Young Adult ,Intellectual Disability ,Genetics ,medicine ,Myopia ,Humans ,Abnormalities, Multiple ,Genetic Predisposition to Disease ,Obesity ,Anhidrosis ,Child ,Genetics (clinical) ,Muscular hypotonia ,Whole Genome Sequencing ,business.industry ,Homozygote ,Retinal Degeneration ,Brain ,medicine.disease ,3. Good health ,VPS13B ,030104 developmental biology ,Codon, Nonsense ,Child, Preschool ,Muscle Hypotonia ,Female ,medicine.symptom ,business - Abstract
Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19-year-old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole-genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene. peerReviewed
- Published
- 2019
18. First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations
- Author
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Lamia Hila, Houweyda Jilani, Syrine Hizem, Yasmina Elaribi, Imen Rejeb, Julia Lauer Zillahrdt, Jamel Chelly, Lamia BenJemaa, Service des Maladies Congénitales et Héréditaires [Tunis, Tunisie], CHU Mongi Slim La Marsa [Tunis, Tunisie], Laboratoire de Génétique Humaine [Tunis, Tunisie], Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM)-Université de Tunis El Manar (UTM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle de biologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), and Bodescot, Myriam
- Subjects
Male ,0301 basic medicine ,Proband ,Microcephaly ,Developmental Disabilities ,Vesicular Transport Proteins ,Case Report ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Bioinformatics ,Compound heterozygosity ,0302 clinical medicine ,Myopia ,Missense mutation ,Exome ,Child ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Genetics (clinical) ,Exome sequencing ,Genetics ,Cohen syndrome ,Retinal Degeneration ,Prognosis ,Pedigree ,3. Good health ,VPS13B ,Child, Preschool ,Muscle Hypotonia ,Female ,lcsh:Internal medicine ,lcsh:QH426-470 ,Biology ,Fingers ,03 medical and health sciences ,Intellectual Disability ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,Humans ,Obesity ,lcsh:RC31-1245 ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Genome, Human ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,Mutation ,Compound heterozygous mutation ,VPS13B gene ,030217 neurology & neurosurgery - Abstract
International audience; BACKGROUND:Cohen syndrome is a rare autosomal recessive developmental disorder that comprises variable clinical features counting developmental delay, pigmentary retinopathy, myopia, acquired microcephaly, truncal obesity, joint hypermobility, friendly disposition and intermittent neutropenia. VPS13B (vacuolar protein sorting 13, yeast, homologue of B) gene is the only gene responsible for Cohen Syndrome, causative mutations include nonsense, missense, indel and splice-site variants. The integrity of the Golgi apparatus requires the presence of the peripheral membrane protein VPS13B that have an essential function in intracellular protein transport and vesicle-mediated sorting.CASE PRESENTATION:In this study, we performed whole exome sequencing (WES) in a Tunisian family with two young cases having developmental delay, hypotonia, autism spectrum disorder, ptosis and thick hair and eyebrows. The proposita presented also pigmentory retinopathy. Compound heterozygous mutation in VPS13B gene was detected by WES. This mutation inherited from healthy heterozygous parents, supports an unpredictable clinical diagnosis of Cohen Syndrome. The proband's phenotype is explained by the presence of compound heterozygous mutations in the VPS13B gene. This finding refined the understanding of genotype-phenotype correlation.CONCLUSIONS:This is the first report of a Tunisian family with Cohen syndrome mutated in the VPS13B gene.
- Published
- 2017
19. Changing facial phenotype in Cohen syndrome
- Author
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Bernard Aral, Nadège Gigot, François-Guillaume Debray, Alice Masurel-Paulet, Patrick Rump, Christel Thauvin-Robinet, Frédéric Huet, Muriel Holder-Espinasse, Marlène Rio, Laurence Duplomb, Patrick Callier, Edward Blair, Anne-Marie Frances, Salima El Chehadeh-Djebbar, Anne Moncla, and Laurence Faivre
- Subjects
Male ,Microcephaly ,Developmental Disabilities ,FEATURES ,facial phenotype ,Vesicular Transport Proteins ,Myopia ,CRITERIA ,HETEROGENEITY ,Child ,Genetics (clinical) ,Genetics ,Cohen syndrome ,Retinal Degeneration ,Hypotonia ,VPS13B ,Phenotype ,medicine.anatomical_structure ,Child, Preschool ,Muscle Hypotonia ,Female ,medicine.symptom ,medicine.medical_specialty ,changing phenotype ,Genetic counseling ,Biology ,Article ,Fingers ,Intellectual Disability ,medicine ,Humans ,Abnormalities, Multiple ,Obesity ,Short philtrum ,Auricle ,NATURAL-HISTORY ,medicine.disease ,Dermatology ,MUTATIONAL SPECTRUM ,GENE ,DELETIONS ,stomatognathic diseases ,Early Diagnosis ,Face ,Mutation ,Square face ,VPS13B gene - Abstract
Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.
- Published
- 2013
20. Search for the best indicators for the presence of a VPS13B gene mutation and confirmation of diagnostic criteria in a series of 34 patients genotyped for suspected Cohen syndrome.
- Author
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El Chehadeh, Salima, Aral, Bernard, Gigot, Nadège, Thauvin-Robinet, Christel, Donzel, Anne, Delrue, Marie-Ange, Lacombe, Didier, David, Albert, Burglen, Lydie, Philip, Nicole, Moncla, Anne, Cormier-Daire, Valérie, Rio, Marlène, Edery, Patrick, Verloes, Alain, Bonneau, Dominique, Afenjar, Alexandra, Jacquette, Aurélia, Heron, Delphine, and Sarda, Pierre
- Subjects
SYNDROMES ,GENETIC mutation ,INTELLECTUAL disabilities ,FACIAL abnormalities ,NEUTROPENIA ,OBESITY - Abstract
Background Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of mental retardation, facial dysmorphism, postnatal microcephaly, truncal obesity, slender extremities, joint hyperextensibility, myopia, progressive chorioretinal dystrophy, and intermittent neutropenia. Patients and methods The aim of the study was to determine which of the above clinical features were the best indicators for the presence of VPS13B gene mutations in a series of 34 patients with suspected Cohen syndrome referred for molecular analysis of VPS13B. Results 14 VPS13B gene mutations were identified in 12 patients, and no mutation was found in 22 patients. The presence of chorioretinal dystrophy (92% vs 32%, p=0.0023), intermittent neutropenia (92% vs 5%, p<0.001), and postnatal microcephaly (100% vs 48%, p=0.0045) was significantly higher in the group of patients with a VPS13B gene mutation compared to the group of patients without a mutation. All patients with VPS13B mutations had chorioretinal dystrophy and/or intermittent neutropenia. The Kolehmainen diagnostic criteria provided 100% sensibility and 77% specificity when applied to this series. Conclusion From this study and a review of more than 160 genotyped cases from the literature, it is concluded that, given the large size of the gene, VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. The follow-up of young patients could be a satisfactory alternative unless there are some reproductive issues. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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