摘要
目的探讨ALS2基因突变导致婴儿起病型上行性遗传性痉挛性截瘫(IAHSP)临床表型及遗传学特点。方法回顾性分析ALS2基因突变致婴儿起病型上行性遗传性痉挛性截瘫先证者临床资料及家系特点,并应用全外显子组测序分析患儿的致病基因,再用Sanger测序进行家系验证,复习相关文献,总结其临床特点及遗传学特征。结果家系1先证者及其姐姐检测到ALS2基因突变位点为c.2687G>A的纯合突变,家系2先证者为c.4221delA和c.575C>T的复合杂合突变;主要表现为运动功能的倒退,下肢痉挛、肌力下降,失去独走能力,合并智力发育存在落后,但头颅影像学无特异性发现;检索到中国知网、万方数据库和PubMed数据库自建库至2023年12月的26篇文献(其中英文25篇,中文1篇),共报道IAHSP77例(包括本文3例)。结论ALS2基因突变致IAHSP,早期症状和痉挛型脑瘫相似,近亲婚配史是纯合突变发生的主要原因,ALS2基因突变多位于RCC1结构域,上肢受累是普遍现象,虽然大多智力正常,但球麻痹和是否可独坐及独立行走决定患儿生活质量,早期干预有重要意义;常规的头颅MRI影像学结果异常率不高,且缺乏特异性。
Objective To investigate the clinical phenotype and genetic characteristics of infantile ascending heredi-tary spastic paraplegia(IAHSP)caused by ALS2 gene mutation.Methods The clinical data and family characteristics of the progenies of ascending hereditary spastic paraplegia caused by ALS2 gene mutation were retrospectively analyzed.Whole exome sequencing(WES)was employed to investigate the pathogenic genes.Sanger sequencing was conducted for familial validation.A comprehensive literature review was conducted to summarize the clinical features,diagnostic and genetic char-acteristics.Results The mutation locus of ALS2 gene was homozygous mutation of c.2687G>A in family 1 and compound heterozygous mutation of c.4221delA and c.575C>T in family 2.The main manifestations were regression of motor function,lower limb spasm,decreased muscle strength,loss of independent walking ability,and backward intellectual development,but no specific findings were found in head imaging.Twenty-six literatures(25 in English and 1 in Chinese)from CNKI,Wan Fang Database and PubMed database from December 2023 were retrieved.A total of 77 IAHSP cases(including 3 in this paper)were reported.Conclusion The early symptoms of IAHSP caused by ALS2 gene mutation are similar to spastic cerebral palsy,and the history of marriage with close relatives is the main cause of homozygous mutation.ALS2 gene mutation is mostly located in the RCC1 domain,and upper limb involvement is a common phenomenon.Although most children have normal intelligence,bulbous palsy and whether they can sit and walk independently determine the quality of life of children.Early intervention is important.Conventional head MRI imaging results showed low abnormal rate and lack of specificity.
作者
朱子豪
华冉
姜俊红
王宝田
吴德
唐久来
杨李
ZHU Zihao;HUA Ran;JIANG Junhong;WANG Baotian;WU De;TANG Jiulai;YANG Li(Pediatric/Pediatric NeuroRehabilitation Center,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China;Pediatrics,Department of Hanshan Hospital,the First Affiliated Hospital of Anhui Medical University(Hanshan County People's Hospital),Maanshan,Anhui 238100,China)
出处
《中国优生与遗传杂志》
2025年第2期363-372,共10页
Chinese Journal of Birth Health & Heredity
