1. A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome.
- Author
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Koehler K, Schuelke M, Hell AK, Schittkowski M, Huebner A, and Brockmann K
- Subjects
- Abnormalities, Multiple diagnosis, Abnormalities, Multiple genetics, Abnormalities, Multiple pathology, Adult, Brain diagnostic imaging, Brain pathology, Child, Child, Preschool, Codon, Nonsense genetics, Developmental Disabilities diagnosis, Developmental Disabilities diagnostic imaging, Developmental Disabilities pathology, Female, Fingers diagnostic imaging, Fingers pathology, Homozygote, Humans, Intellectual Disability diagnosis, Intellectual Disability diagnostic imaging, Intellectual Disability pathology, Male, Microcephaly diagnosis, Microcephaly diagnostic imaging, Microcephaly pathology, Muscle Hypotonia diagnosis, Muscle Hypotonia diagnostic imaging, Muscle Hypotonia pathology, Myopia diagnosis, Myopia diagnostic imaging, Myopia pathology, Obesity diagnosis, Obesity diagnostic imaging, Obesity pathology, Retinal Degeneration diagnosis, Retinal Degeneration diagnostic imaging, Retinal Degeneration pathology, Whole Genome Sequencing, Young Adult, Developmental Disabilities genetics, Fingers abnormalities, Genetic Predisposition to Disease, Intellectual Disability genetics, Microcephaly genetics, Muscle Hypotonia genetics, Myopia genetics, Obesity genetics, Retinal Degeneration genetics, Vesicular Transport Proteins genetics
- 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., (© 2019 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.)
- Published
- 2020
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