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A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome
Author(s) -
Koehler Katrin,
Schuelke Markus,
Hell Anna K.,
Schittkowski Michael,
Huebner Angela,
Brockmann Knut
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61435
Subject(s) - nonsense mutation , hypotonia , medicine , genetics , nonsense , short stature , phenotype , compound heterozygosity , mutation , missense mutation , endocrinology , gene , pediatrics , biology
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.