GALNS基因突变所致黏多糖贮积症ⅣA型3个家系遗传学分析  

Genetic analysis of three pedigrees with mucopolysaccharidosis type V A caused by GALNS mutation

作　　者：张冰 杨科 王莉 张玉薇 娄桂予 祁娜 雷星星 王凤阳 廖世秀 ZHANG Bing;YANG Ke;WANG Li;ZHANG Yuwei;LOU Guiyu;QI Na;LEI Xingxing;WANG Fengyang;LIAO Shixiu(Instituteof Medical Genetics,Henan Provincial People'sHospital,Zhengzhou University People's Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]河南省人民医院医学遗传研究所郑州大学人民医院,河南郑州450003

出　　处：《中华实用诊断与治疗杂志》2025年第2期130-133,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省科技攻关计划项目(232102521028);河南省医学科技攻关计划联合共建项目(LHGJ20240051)。

摘　　要：目的 分析3个黏多糖贮积症ⅣA型家系的临床资料,探讨其遗传学病因。方法 2020年1月-2022年12月河南省人民医院进行遗传咨询的黏多糖贮积症ⅣA型3个家系,收集先证者患儿临床资料,并对3例先证者及其父母进行全外显子组测序。针对全外显子组测序筛选出的可疑突变位点,采用Sanger测序对3个家系先证者及其父母进行验证。应用SIFT、Polyphen、MutationTaster软件预测突变致病性;检索人类基因突变数据库,查看GALNS基因突变报道情况;依据ACMG指南对突变进行致病性评级。结果 3例先证者均表现为身材矮小、骨骼畸形,血N-乙酰半乳糖胺-6-硫酸酯酶活性降低。先证者1存在GALNS基因(NM_000512)c.892G>T(父源)及Exon1-4del(母源)复合杂合突变;先证者2存在GALNS基因(NM_000512)c.1019G>A(父源)及c.1166C>T(母源)复合杂合突变;先证者3存在GALNS基因(NM_000512)c.281G>T(父源)及c.688T>G(母源)复合杂合突变。SIFT、Polyphen、MutationTaster软件分析结果显示,GALNS基因c.1019G>A、c.1166C>T、c.281G>T、c.688T>G突变有致病性。GALNS基因c.1019G>A、c.281G>T、c.688T>G为文献已报道的致病性突变;c.892G>T、Exon1-4del、c.1166C>T为未报道的新突变,ACMG指南评级均为可能致病。结论 GALNS基因c.892G>T及Exon1-4del复合杂合突变、c.1019G>A及c.1166C>T复合杂合突变、c.281G>T及c.688T>G复合杂合突变可能是该3个家系患儿罹患黏多糖贮积症ⅣA型的遗传学病因。Objective To analyze the clinical data of three pedigrees with mucopolysaccharidosis(MPS)type IV A and to investigate the genetic etiology.Methods The clinical data were collected from three pedigrees with MPS type IV A who received genetic counseling in Henan Provincial People's Hospital from January 2020 to December 2022.All three probands and their parents were performed whole exome sequencing,and the suspected variants were validated by Sanger sequencing.SIFT,Polyphen and MutationTaster were used to predict the pathogenicity of mutations.The human gene mutation database was searched and the mutation reports of GALNS gene was checked.The mutations were graded for pathogenicity according to ACMG guidelines.Results All three probands had short stature,skeletal deformities,and low blood N-acetylgalactosamine-6-sulfatase activity.Proband 1 had compound heterozygous mutations in GALNS gene(NM_000512),including c.892G>T(inherited from the father)and Exonl-4del(from the mother).Proband 2 had compound heterozygous mutations in GALNS gene(NM_000512),including c.1019G>A(from the father)and c.1166C>T(from the mother).Proband 3 had compound heterozygous mutations in GALNS gene(NM_0o0512),including c.281G>T(from the father)and c.688T>G(from the mother).SIFT,Polyphen and MutationTaster analysis results showed that the c.1019G>A,c.1166C>T,c.281G>T and c.688T>G mutations in GALNS gene were pathogenic.GALNS gene c.1019G>A,c.281G>T and c.688T>G were the known pathogenic mutations in the literature.GALNS gene c.892G>T,Exonl-4del and c.1166C>T were the novel mutations and all graded as likely pathogenic by ACMG.Conclusion The compound heterozygous mutations of c.892G>T and Exonl-4del,c.1019G>A and c.1166C>T,and c.281G>T and c.688T>G in GALNS gene may be the main genetic etiology of these three pedigreesaffectedwithMPStypeIVA.

关 键 词：黏多糖贮积症ⅣA型 GALNS基因 全外显子组测序 骨骼畸形 

分 类 号：R73[医药卫生—肿瘤]