五个遗传性痉挛性截瘫家系的临床特征及基因变异分析  

Clinical characteristics and variant analysis of five pedigrees with hereditary spastic paraplegia

作　　者：解燕川 夏艳洁 孙宗立[1] 谷雷[1] 白周现 孔祥东[2] Xie Yanchuan;Xia Yanjie;Sun Zongli;Gu Lei;Bai Zhouxian;Kong Xiangdong(Department of Central Laboratory,the First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan 471003,China;Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450000,China)

机构地区：[1]河南科技大学临床医学院,河南科技大学第一附属医院中心实验室,洛阳471003 [2]郑州大学第一附属医院遗传与产前诊断中心,450000

出　　处：《中华医学遗传学杂志》2020年第7期709-712,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002203)。

摘　　要：目的探讨遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)家系的临床及遗传学特征。方法收集5个HSP家系患者的临床资料,应用高通量测序法筛查、Sanger测序法验证基因变异位点。结果家系1、2的先证者SPAST基因分别存c.1196C>T杂合变异、c.1523T>A杂合变异;家系3先证者FA2H基因存在c.61G>C和c.688G>A复合杂合变异;家系4先证者SPG11基因剪接区存在c.6812+4_6812+7delAGTA和c.915delT复合杂合变异;家系5先证者SPG7基因存在c.1703_1704delAG和剪接区c.1937-1G>C复合杂合变异。通过美国医学遗传学与基因组学学会遗传变异分类标准与指南评估,这些变异均为可能的致病变异。其中SPAST基因c.1523T>A、FA2H基因c.61G>C、SPG11基因剪接区c.6812+4_6812+7delAGTA、c.915delT、SPG7基因c.1703_1704delAG及剪接区c.1937-1G>C变异均为未报道过的新变异。结论家系1、2为常染色体显性遗传性痉挛性截瘫4型,其中家系2为不完全外显;家系3、4、5分别为常染色隐性遗传性痉挛性截瘫35型、11型、7型。上述发现为HSP的临床诊断及遗传咨询提供了依据。Objective To explore the clinical and genetic characteristics of five pedigrees affected with hereditary spastic paraplegia(HSP).Methods Clinical data of the five pedigrees was collected,and high-throughput sequencing was carried out to detect potential variants.Sanger sequencing were used to verify the results.Results The probands of pedigree 1 and 2 were found to harbor heterozygous SPAST gene variants,namely c.1196C>T and c.1523T>A.The proband of pedigree 3 harbored compound heterozygous variants of FA2H gene(c.61G>C and c.688G>A).Proband from pedigree 4 harbored compound heterozygous variants of SPG11 gene(c.6812+4_6812+7delAGTA and c.915delT).The proband of pedigree 5 harbored compound heterozygous variants of SPG7 gene(c.1703_1704delAG and c.1937-1G>C).Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,all variants were predicted to be likely pathogenic.Among these,SPAST gene c.1523T>A,FA2H gene c.61G>C,SPG11 gene splicing region c.6812+4_6812+7delAGTA,c.915delT,SPG7 gene c.1703_1704delAG and splicing region c.1937-1G>C variants were unreported previously.Conclusion The probands of pedigrees 1 and 2 were diagnosed with autosomal dominant hereditary spastic paraplegia type 4,for which pedigree 2 showed incompletely penetrance.Pedigrees 3,4,and 5 were diagnosed with autosomal recessive hereditary spastic paraplegia type 35,11 and 7,respectively.Above result provided a reference for clinical diagnosis and genetic counseling for the affected pedigrees.

关 键 词：遗传性痉挛性截瘫 SPAST基因 FA2H基因 SPG11基因 SPG7基因 高通量测序 

分 类 号：R596.2[医药卫生—内科学]