The Laboratory of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, University of South China, Changsha, 410007, China.
Department of Child Healthcare, Hunan Children's Hospital, University of South China, Changsha, 410007, Hunan, China.
BMC Med Genet. 2019 Nov 21;20(1):187. doi: 10.1186/s12881-019-0920-x.
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.
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.
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.
Cohen 综合征（CS）是一种罕见的发育性疾病，具有明显的临床异质性。VPS13B 是唯一与 CS 相关的基因。在中国，仅报道过少数散发性 CS 病例。
本研究调查了一个中国家庭，该家庭中有两个受发育迟缓及智力障碍影响的后代患者。对该家庭进行外显子组测序，发现 VPS13B 存在复合杂合突变，符合常染色体隐性遗传疾病。剪接突变 c.3666 + 1G > T（exon 24）和无义突变 c. 9844 A > T:p.K3282X（exon 54）为新发现的突变。我们再次对该家庭进行了回访，发现两名患者均存在小头畸形、发育迟缓、中性粒细胞减少和近视，性格友好，这些均与 CS 表型一致。我们还发现两名患者均存在弓形掌纹，而其父母均无此特征。因此，对中国人群中报道的 VPS13B 突变进行了相应的回顾。
本研究发现了 Cohen 综合征中的两个新的 VPS13B 突变。CS 患者中弓形掌纹的发现扩展了 CS 的表型谱。
