遗传性痉挛性截瘫家系的临床表现与致病基因分析  

Clinical manifestation and genetics analysis of hereditary spastic paraplegia families

作　　者：张钏[1] 惠玲 周秉博 郑雷[1] 王玉佩 田芯瑗 马盼盼 郝胜菊[1] 达振强 ZHANG Chuan;HUI Ling;ZHOU Bingbo;ZHENG Lei;WANG Yupei;TIAN Xinyuan;MA Panpan;HAO Shengju;DA Zhenqiang(Gansu Provincial Maternity and Child-care Hospital(Central Hospital of Gansu Province),Medical Genetics Center,Gansu Provincial Clinical Medical Research Center of Default Defects and Rare Diseases,Lanzhou 730050,China)

机构地区：[1]甘肃省妇幼保健院(甘肃省中心医院),医学遗传中心,甘肃省出生缺陷与罕见病临床医学研究中心,兰州730050

出　　处：《中国神经精神疾病杂志》2025年第3期129-134,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：甘肃省科技计划资助项目(编号:22YF7FA094);兰州市科技计划项目(编号:2021-1-182);甘肃省卫生行业计划项目(编号:GSWSKY2022-33);甘肃省科技厅创新基地及人才计划(编号:21JR7RA680);医院科研基金项目资助(编号:GMCCH2024-2-2);甘肃省自然科学基金(编号:23JRRA1378,23JRRA1752)。

摘　　要：目的对3个遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)患者家系的临床表现及致病基因进行分析。方法对甘肃省妇幼保健院(甘肃省中心医院)收集的3个HSP患者家系进行基因分析。结果家系1中先证者为FA2H c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)纯合变异导致的常染色体隐性痉挛性截瘫35型,家系2中的先证者为AP4B1 c.1399G>T(p.Glu467Ter)纯合变异导致的常染色体隐性痉挛性截瘫47型,家系3中先证者为SPG11 c.7023C>G(p.Tyr2341Ter)的纯合变异导致的常染色体隐性痉挛性截瘫11型。其中,AP4B1 c.1399G>T(p.Glu467Ter)位点为尚未报告的变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)指南,该变异的致病性评级为致病性变异。结论本研究丰富了HSP致病基因AP4B1的变异谱,为提高临床对HSP患者的认识与诊断能力提供了基础性数据。Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

关 键 词：遗传性痉挛性截瘫 基因变异 基因诊断 干预治疗 临床诊断 常染色体隐性 FA2H基因 AP4B1基因 SPG11基因 

分 类 号：R745.4[医药卫生—神经病学与精神病学]