GLRA2基因变异致X连锁智力障碍综合征Pilorge型1例

X-linked intellectual disability syndrome caused by GLRA2 gene mutation:A case report

目的探讨GLRA2基因相关X连锁智力障碍综合征Pilorge型(MRXSP)的临床表型与遗传学特点。方法回顾性分析2023年在潍坊市妇幼保健院就诊的1例GLRA2基因变异患儿的临床资料及全外显子组测序(WES)结果。以“GLRA2”为关键词检索中国知网、万方、OMIM和PubMed数据库相关文献,总结GLRA2基因变异特点以及X连锁智力障碍综合征Pilorge型的临床特点。结果患儿,男,1岁4个月,因“未能独立站立和行走”就诊,语言表达能力差,智力测验显示发育商(DQ)为64分,头颅MRI提示脑损伤后遗改变合并皮质发育不良,考虑诊断为“全面性发育迟缓”。父母体健,否认家族性遗传病史。WES显示先证者GLRA2基因第7号外显子携带新发嵌合变异c.925C>A(p.Pro309Thr),属于半合子变异,经Sanger验证父母均未发现该变异。该变异尚未见报道,根据美国医学遗传学与基因组学学会(ACMG)指南判断为“可能致病”。结论当患儿表现为全面性发育迟缓,包括智力、语言、行为和社交方面的异常,以及运动不协调、癫痫或眼部异常时,应考虑MRXSP,建议进行基因检测,如发现GLRA2基因变异,可明确诊断。

Objective To investigate the clinical and genetic characteristics of the Pilorge type of X-linked syndromic intellectual developmental disorder(MRXSP)related to the GLRA2 gene.Methods A retrospective analysis was conducted on the clinical data and whole-exome sequencing results of a male child with GLRA2 gene mutation who visited the Weifang Maternal and Child Health Hospital in 2023.Relevant literature was searched using the keywords“GLRA2”in the China National Knowledge Infrastructure(CNKI),Wanfang,OMIM and PubMed databases to summarize the characteristics of GLRA2 gene variations and the clinical features of MRXSP.Results The proband,a boy,1 year and 4 months old,was presented with the inability to stand or walk independently.He exhibited poor language expression ability,with a developmental quotient(DQ)of 64 on intellectual testing,and cranial MRI suggested residual changes after brain injury combined with cortical dysplasia,leading to a diagnosis of“global developmental delay”.Both parents were healthy and denied a family history of hereditary diseases.Whole exome sequencing(WES)revealed a de novo mosaic mutation c.925C>A(p.Pro309Thr)in the 7th exon of the GLRA2 gene in the proband,which was confirmed to be a hemizygote variation by Sanger sequencing,and neither parent was found to carry this variation.This variant has not been reported previously and was classified as“likely pathogenic”according to the American College of Genetics and Genomics(ACMG)guidelines.Conclusion When a child suffers from global developmental delay,including abnormalities in intellectual,language,behavioral,and social aspects,as well as motor incoordination,seizures,or ocular abnormalities,MRXSP should be considered.Genetic testing is recommended,and the diagnosis can be confirmed if GLRA2 gene mutations are detected.