CDK5RAP2小头畸形与先天性白内障之间的新关联。

A new association between CDK5RAP2 microcephaly and congenital cataracts.

作者信息

Alfares Ahmed, Alhufayti Ibtihal, Alsubaie Lamia, Alowain Mohammed, Almass Rawan, Alfadhel Majid, Kaya Namik, Eyaid Wafaa

机构信息

Department of Pediatrics, College of Medicine, Qassim University, Qassim, Saudi Arabia.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

出版信息

Ann Hum Genet. 2018 May;82(3):165-170. doi: 10.1111/ahg.12232. Epub 2017 Dec 22.

DOI:10.1111/ahg.12232

PMID:29271474

Abstract

INTRODUCTION

Primary microcephaly type 3 is a genetically heterogeneous condition caused by a homozygous or compound heterozygous mutation in CDK5 regulatory subunit associated protein 2 (CDK5RAP2) and characterized by reduced head circumference (<5th percentile) with additional phenotypes varying from pigmentary abnormalities to sensorineural hearing loss. Until now, congenital cataracts have not been reported in patients with primary microcephaly type 3.

CLINICAL REPORT

We report multiple affected family members from a consanguineous Saudi family with microcephaly and congenital cataracts. We utilized a next-generation sequencing-based microcephaly gene panel that revealed a CDK5RAP2 variant (c.4055A>G; p.Glu1352Gly) as the most plausible candidate for the likely etiology in this family. Then we performed family segregation analysis using Sanger sequencing, autozygosity mapping, and whole exome sequencing, all of which revealed no other possible disease-causing variants.

CONCLUSION

Here we report on a new clinical manifestation of CDK5RAP2 and expand the phenotype of primary microcephaly type 3.

摘要

引言

3型原发性小头畸形是一种基因异质性疾病，由细胞周期蛋白依赖性激酶5调节亚基相关蛋白2（CDK5RAP2）的纯合或复合杂合突变引起，其特征为头围减小（<第5百分位数），并伴有从色素异常到感音神经性听力损失等多种其他表型。迄今为止，尚未有3型原发性小头畸形患者出现先天性白内障的报道。

临床报告

我们报告了一个来自沙特近亲家庭的多名患病家庭成员，他们患有小头畸形和先天性白内障。我们使用了基于下一代测序的小头畸形基因检测板，结果显示一个CDK5RAP2变体（c.4055A>G；p.Glu1352Gly）是这个家族可能病因的最合理候选基因。然后我们使用桑格测序、纯合性定位和全外显子测序进行家系分离分析，所有这些分析均未发现其他可能的致病变体。