一例伴脑桥和小脑发育不良的智力障碍和小头畸形患儿的临床表型及基因变异分析  

Clinical and genetic analysis of a child with mental retardation and microcephaly with pontine and cerebellar hypoplasia

作　　者：王紫微 李闯 赵妍[2] 李岭 吕远[1] 崔红[1] Wang Ziwei;Li Chuang;Zhao Yan;Li Ling;Lyu Yuan;Cui Hong(Department of Gynecology and Obstetrics,Shengjing Hospital Affiliated to China Medical University,Key Laboratory of Maternal-Fetal Medicine of Liaoning Province,Shenyang,Liaoning 110004,China;Department of Genetics,Shenyang Women and Children’s Hospital,Shenyang,Liaoning 110011,China;State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]中国医科大学附属盛京医院妇产科辽宁省母胎医学重点实验室,沈阳110004 [2]沈阳市妇婴医院遗传科,110011 [3]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《中华医学遗传学杂志》2021年第10期985-988,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1例伴脑桥和小脑发育不良的智力障碍和小头畸形(mental retardation and microcephaly with pontine and cerebellar hypoplasia,MICPCH)的患儿及其家系成员进行临床表型及基因变异分析。方法详细记录患儿的临床表型,对其进行全外显子组测序(whole exome sequencing,WES),并用Sanger测序对患儿及其家系成员进行验证。结果患儿临床表现为运动障碍、发育滞后、小脑发育不全、双侧听觉障碍。WES检测提示其携带CASK基因c.1641_1644delACAA(p.Thr548Trpfs*69)杂合致病变异。Sanger测序提示,患儿父母均未携带同样的变异。结论CASK基因致病变异可能是患儿发生MICPCH的分子基础。WES有助于明确神经系统发育异常的诊断,为遗传咨询提供依据。Objective To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia(MICPCH).Methods Clinical phenotype of the child was reviewed.Whole exome sequencing was carried out for the child.Candidate variant was verified by Sanger sequencing of the family member.Results The proband manifested dyskinesia,development delay,cerebellar hypoplasia and bilateral hearing impairment.WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA(p.Thr548Trpfs*69)variant of the CASK gene,which was verified by Sanger sequencing to be a de novo variant.Conclusion The c.1641_1644delACAA(p.Thr548Trpfs*69)variant of the CASK gene probably underlay the MICPCH in the proband.Above finding has provided a basis for genetic counseling.WES should be considered for the diagnosis of neurological dysplasia.

关 键 词：伴脑桥和小脑发育不良的智力障碍和小头畸形 CASK基因 移码突变 全外显子组测序 

分 类 号：R742[医药卫生—神经病学与精神病学]