DMD基因突变的孤独症谱系障碍儿童1例报告并文献复习  

Autism Spectrum Disorder Caused by DMD Gene Mutation:a Case Report and Literature Review

作　　者：詹国栋 李建英 游聪 周丽容 刘映平 刘宇翀 邹小兵 岑超群 HAN Guo-dong;LI Jian-ying;YOU Cong;ZHOU Li-rong;LIU Ying-ping;LIU Yu-chong;ZOU Xiao-bing;CEN Chao-qun(Child Development Behavior Center,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院儿童发育行为中心,广州510630

出　　处：《实用临床医学（江西）》2024年第3期47-54,59,共9页Practical Clinical Medicine

基　　金：科学技术部科技创新2030——“脑科学与类脑研究”重大项目,脑疾病临床研究大数据与样本库平台建设(2021ZD0200800)。

摘　　要：目的对DMD基因突变的1例6岁孤独症谱系障碍(autism spectrum disorder,ASD)男性患儿进行报告,并通过文献回顾探讨DMD基因缺陷患者的ASD共患率,分析该类患者的遗传学特点,以提高对该亚型ASD的认识。方法利用染色体微阵列分析技术对ASD先证者进行检测,多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对候选突变进行家系验证。对患儿临床表型与基因型进行分析,并系统复习DMD基因突变与ASD的相关文献。结果患儿存在DMD基因arr[hg19]Xp21.1(31,518,750-31,878,971)×0微缺失,涉及DMD基因48—55号外显子,MLPA验证提示该缺失遗传自无疾病表型的母亲。文献回顾表明:贝克尔肌营养不良症(Becker muscular dystrophy,BMD)患者ASD的共患率在0.00%(0/17)~11.43%(8/70),而杜氏肌营养不良症(Duchenne muscular dystrophy,DMD)在0.0%(0/50)~54.5%(30/55)。BMD与DMD相比,前者所有队列ASD共患率的中位数(3.6%)低于后者的中位数(6.4%),但差异无统计学意义。DMD基因突变的位置与ASD发病是否相关存在争议。结论DMD基因48—55号外显子缺失可能是患儿存在BMD和ASD的共同病因。DMD基因的基因型与ASD临床表型的关系需要进一步的研究。Objective To explore the co-prevalence rates of ASD in patients with DMD gene defects through a case study of a 6-year-old male child with autism spectrum disorder(ASD)who had a mutation in the DMD gene and a literature review,and to analyze genetic characteristics of such patients in order to improve the understanding of this subtype of ASD.Methods Chromo-somal microarray analysis was utilized to detect ASD precursors,and multiplex ligation-dependent probe amplification(MLPA)was used to validate the family lines for candidate mutations.The clinical phenotype and genotype of the patient were analyzed,and the literature on DMD mutations and ASD was systematically reviewed.Results The child was found to have a arr[hg19_]Xp21.1(31,518,750-31,878,971)×0 microdeletion involving exons 48-55 of the DMD gene.MLPA validation indicated that the deletion was inherited from his mother without a disease pheno-type.A literature review revealed that the co-prevalence of ASD in patients with Becker muscular dystrophy(BMD)ranged from 0%(0/17)to 11.43%(8/70),while that of Duchenne muscular dystrophy(DMD)ranged from 0%(0/50)to 54.5%(30/55).The median co-prevalence of ASD for all cohorts of BMD(3.6%)was lower than the median co-prevalence for all cohorts of DMD(6.4%),but the difference was not statistically significant.Whether the location of the DMD gene mutations is associated with ASD pathogenesis is controversial.Conclusion The results suggest that the deletion of exon 48-55 of the DMD gene may be a common etiology for the presence of BMD and ASD in affected children.The relationship between the genotype of the DMD gene and the clinical phenotype of ASD requires further investigation.

关 键 词：DMD基因 孤独症谱系障碍 杜氏肌营养不良症 贝克尔肌营养不良症 基因变异 

分 类 号：R748[医药卫生—神经病学与精神病学]