A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome
A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome
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DOI：
10.1002/ajmg.a.61435
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发表时间：
2019-12-11
影响因子：
2
通讯作者：
Brockmann, Knut
中科院分区：
文献类型：
--
作者：
Koehler, Katrin;Schuelke, Markus;Brockmann, Knut
科恩综合征（CS）是一种罕见的常染色体隐性遗传病，与液泡蛋白分选13同源物B（VPS 13 B;以前称为COH 1）基因突变有关。核心临床表型包括特征性面部完形、显著发育迟缓和近视。另外，非强制性特征包括肥胖、小头畸形、身材矮小、肌肉张力减退、脊柱侧凸、手和脚狭窄、进行性视网膜病变以及中性粒细胞减少症。在这里，我们报告了一个新的纯合无义突变VPS 13 B基因和以前未描述的临床特征，在一个19岁的女性发育迟缓，智力残疾，和一个特定的面部外观。患者表现出与CS一致的几个特征。此外，父母观察到先天性无泪症和无汗症持续到青春期开始。根据临床表型未确立诊断。我们进行了全基因组测序，并确定了一个新的纯合无义突变c.62T>G（NM_152564.4），p.（Leu21*）。我们的研究结果扩展了以前报道的CS表型。我们的结论是短暂的青春期前无泪症和无汗症是CS表型谱的一部分，与VPS 13 B基因中的一种新的纯合无义突变相关。
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.