Centre for Reproduction and Genetics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Centre for Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.
J Int Med Res. 2020 Feb;48(2):300060519877997. doi: 10.1177/0300060519877997. Epub 2019 Sep 26.
To confirm diagnosis and explore the genetic aetiology in a Chinese patient suspected to have Cockayne syndrome (CS).
The patient was clinically examined, and the patient and her biological parents underwent genetic analysis using whole exome sequencing (WES) and Sanger sequencing. The foetus of the patient's mother underwent prenatal diagnostic Sanger sequencing using amniotic fluid obtained at 19 weeks' gestation.
Clinical examination of the patient showed developmental delay, progressive neurologic dysfunction and premature aging. Two compound, heterozygous ERCC excision repair 6, chromatin remodelling factor () gene mutations were detected in the proband by WES and confirmed by Sanger sequencing, comprising a known paternal nonsense mutation (c.643G > T, p.E215X) and a novel maternal short insertion and deletion mutation (c.1614_c.1616delGACinsAAACGTCTT, p.K538_T539delinsKNVF). The patient was consequently diagnosed with CS type I. The foetus of the patient's mother was found to carry only the maternally-derived c.1614_c.1616delGACinsAAACGTCTT variant.
This study emphasized the value of WES in clinical diagnosis, and enriched the known spectrum of gene mutations.
对一名疑似 Cockayne 综合征（CS）的中国患者进行确诊并探究其遗传病因。
对患者进行临床检查，对患者及其亲生父母进行全外显子组测序（WES）和 Sanger 测序的基因分析。对患者母亲的胎儿进行产前诊断性 Sanger 测序，采用羊水样本，取自妊娠 19 周时。
对患者的临床检查显示其存在发育迟缓、进行性神经功能障碍和早衰。通过 WES 检测到先证者存在两个复合杂合 ERCC 切除修复 6、染色质重塑因子（）基因突变，通过 Sanger 测序证实，包括一个已知的父源无义突变（c.643G>T，p.E215X）和一个新的母源短插入和缺失突变（c.1614_c.1616delGACinsAAACGTCTT，p.K538_T539delinsKNVF）。因此，患者被诊断为 CS Ⅰ型。患者母亲的胎儿仅携带母源来源的 c.1614_c.1616delGACinsAAACGTCTT 变异。
本研究强调了 WES 在临床诊断中的价值，并丰富了已知的 基因突变谱。
