[因PCDH15基因新型复合杂合变异导致的中国Usher综合征家系的遗传分析及产前诊断]
[Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene].
作者信息
Yang Ke, Zhang Yuwei, Lou Guiyu, Qi Na, Zhang Bing, Kang Bing, Lei Xingxing, Liao Shixiu
机构信息
Medical Genetic Institute of Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.
出版信息
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Mar 10;39(3):305-308. doi: 10.3760/cma.j.cn511374-20210309-00201.
OBJECTIVE
To analyze the clinical features and genetic variant in a patient with Usher syndrome.
METHODS
Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.
RESULTS
The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.
CONCLUSION
The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
目的
分析一名患有Usher综合征患者的临床特征和基因变异情况。
方法
对该患者进行全外显子组测序。通过对其父母及胎儿进行Sanger测序验证可疑变异。
结果
先证者被发现携带PCDH15基因（NM_033056）的复合杂合变异c.17_18insA（p.Tyr6Ter*）和c.4095_4096insA（p.Arg1366Lys fs*38），分别遗传自其父亲和母亲。在100名健康对照中未检测到相同变异。根据美国医学遗传学与基因组学学会的指南，这两个变异均被预测为致病性变异（PVS1+PM2+PP4）。通过产前诊断，发现其胎儿携带c.4095_4096insA变异。出生后，该儿童通过了新生儿听力筛查测试，1岁后未发现听觉和视觉功能异常。
结论
PCDH15基因的复合杂合变异c.17_18insA（p.Tyr6Ter*）和c.4095_4096insA（p.Arg1366Lys fs*38）可能是该先证者Usher综合征的病因。
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