NSRP1基因变异导致的神经发育障碍家系的遗传学分析  

Genetic analysis of families with neurodevelopmental disorders caused by NSRP1 gene variant

作　　者：李明[1] 李淑元[1] 王彦林[1] LI Ming;LI Shuyuan;WANG Yanlin(International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200030,China)

机构地区：[1]上海交通大学医学院附属国际和平妇幼保健院生殖遗传科,上海200030

出　　处：《中国优生与遗传杂志》2024年第3期541-544,共4页Chinese Journal of Birth Health & Heredity

基　　金：上海市2022年度“科技创新行动计划”医学创新研究专项项目(22Y11906700)。

摘　　要：目的 探究神经发育障碍患儿的分子遗传学病因,为家庭再生育提供优生指导。方法 对先证者男孩及其父母3人进行家系全外显子组测序(trio-WES)分析,利用Sanger测序对变异候选位点进行验证,并对再次妊娠胎儿产前羊水样本进行检测。结果 家系全外显子组测序(trio-WES)结果提示先证者携带NSRP1基因的纯合移码变异c.1272dup(p.Lys425GlufsTer5),父母均为杂合子携带者。无其他符合遗传模式并且可解释患者表型的可疑变异。产前诊断提示胎儿未携带上述变异。根据美国医学遗传学与基因组学学会(ACMG)变异评级指南,该变异被归类为可能致病变异。NSRP1纯合变异导致的神经发育障碍伴痉挛、癫痫和大脑异常疾病,目前国际仅6例疾病患儿报道,国内尚未见病例报道。结论 该家系为国内首个NSRP1纯合致病变异导致的神经发育障碍家系。本研究明确了先证者男孩神经发育障碍分子学病因,有助于准确的遗传咨询和再发风险评估,为该家庭再生育提供了很好的生育指导。Objective To explore the molecular genetic etiology for a child with neurodevelopmental disorders and provide eugenic guidance for family reproduction.Methods Whole exome sequencing(WES)analysis was carried out for the proband and his parents,and candidate variants were verified by Sanger sequencing of the proband and her parents.Additionally,prenatal diagnosis was provided to her mother by amniocentesis upon her subsequent pregnancy.Results A homozygote null variant,c.1272dup(p.Lys425GlufsTer5),was identified in the NSRP1 gene by trio-WES,while both parents were heterozygous carriers of the mutation.There were no other suspected variants that matching the genetic pattern and could explain the patient’s phenotype.Prenatal diagnosis indicated that the fetus did not carry the aforementioned variant.According to the American College of Medical Genetics and Genomics(ACMG)variant classification guidelines,this variant is classified as a likely pathogenic variant.Neurodevelopmental disorders characterized by spasticity,epilepsy,and brain abnormalities caused by homozygous variation of NSRP1 have only been reported in six cases internationally,with no reported cases in China to date.Conclusion This is the first family with neurodevelopmental disorder caused by homozygous variant of NSRP1 in China.This study elucidates the molecular etiology of neurodevelopmental disorders in the proband boy,providing valuable insights for precise genetic counseling,recurrence risk assessment,and offering sound reproductive guidance for the family's decision to have a second child.

关 键 词：神经发育障碍 癫痫 全外显子组测序 NSRP1基因 

分 类 号：R748[医药卫生—神经病学与精神病学]