IMPDH1基因新变异导致的视网膜色素变性1例患者的遗传学分析

Analysis of a patient with Retinitis pigmentosa due to a novel variant of IMPDH1 gene

目的探讨1例常染色体显性遗传视网膜色素变性(RP)患者的遗传学病因。方法选取2019年9月就诊于甘肃省妇幼保健院的1例男性RP患者作为研究对象,回顾性分析其临床资料。对患者及其父母进行全外显子组测序,对候选变异进行Sanger测序家系验证,并用生物信息学软件分析其致病性。结果患者为29岁男性,自幼出现夜盲、弱视、视野缺陷及视盘异常。基因测序结果显示其存在IMPDH1:c.942G>C(p.Lys314Asn)杂合变异,其母亲携带该变异,父亲为野生型。根据美国医学遗传学与基因组学学会相关指南,c.942G>C(p.Lys314Asn)评级为可能致病性变异(PM1+PM2_Supporting+PP3+PP1)。结论IMPDH1:c.942G>C(p.Lys314Asn)可能为该RP患者的遗传学病因。

Objective To explore the genetic basis for a patient with autosomal dominant retinitis pigmentosa(RP).Methods A male patient with RP treated at Gansu Provincial Maternal and Child Health Care Hospital in September 2019 was selected as the study subject.Clinical data was collected.Peripheral blood samples of the patient and his parents were subjected to whole exome sequencing(WES).Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results The patient,a 29-year-old male,developed night blindness,amblyopia,visual field defects and optic disc abnormalities since childhood.Gene sequencing revealed that he has harbored a heterozygous c.942G>C(p.Lys314Asn)variant of the IMPDH1 gene,which was inherited from his mother,whilst his father was of the wild type.Based on the guidelines from the American College of Medical Genetics and Genomics,the c.942G>C variant was predicted as likely pathogenic(PM1+PM2_Supporting+PP3+PP1).Conclusion The c.942G>C(p.Lys314Asn)variant in the IMPDH1 gene probably underlay the RP in this patient.