MBD5热点变异S147*致婴儿期癫痫和全面发育迟缓1例的遗传学分析  

Genetic analysis of a patient with epilepsy and global developmental delay in infancy caused by recurrent MBD5 S147*

作　　者：江晨银 尤仲敏[1] 刘玉峰[1] 朱杰[1] JIANG Chenyin;YOU Zhongmin;LIU Yufeng;ZHU Jie(Department of Child Rehabilitation Medicine,Maternal and Child Healthy Hospital of Hubei Province,Wuhan,Hubei 430070,China)

机构地区：[1]湖北省妇幼保健院儿童康复医学科,湖北武汉430070

出　　处：《中国优生与遗传杂志》2023年第5期1051-1055,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的 描述新的1例MBD5热点变异S147*导致的临床特征,探索该热点变异的基因型-表型关联。方法 结合临床常规及神经康复发育专科检查,利用家系全外显子组测序(trioWES)检测与表型相关的基因变异。利用“MDB5”及其别名“MRD1”和“Methyl-CpG Binding Domain Protein 5”,分别在万方、PubMed、GeneCards及OMIM、ClinVar和Varsome数据库中搜索国内外的相关遗传性疾病报道。结果 男性患儿,诊断时7个月零25天。临床表现为6月龄时起病的全身强直-肌阵挛发作(GTCS)和全面发育迟缓(GDD)。trioWES检出患儿新发MBD5基因无义突变NM_018328.4:c.440C>A/p.S147*,为多个患者中发现的热点变异(dbSNP:rs886041003)。本例表型与先前报道S147*案例相似,且与已报道位于同一蛋白链区域(AA123-152)C端下游T157Qfs4的案例表型高度一致。结论 本例MBD5S147*的报道丰富了这一热点变异的关联表型。与已报道点突变案例的临床特征比较发现,MBD5蛋白质区域AA123-152可能有与MRD1表型潜在相关的未知功能,这有待深入探索。Objective To describe the clinical features caused of a new patient by recurrent variant MBD5 S147*and discover the genotype-phenotype association of cases of MRD1 due to MBD5 single nucleic variant.Methods Combined with clinical routine examination and neuro developmental specialist examination,use trio whole-exome sequencing(trioWES)to detect genetic variation related to phenotype.Use"MDB5","MRDI"(alias)and "Methyl-CpG Binding Domain Protein 5"to search related domestic and foreign genetic disease reports Wanfang database,PubMed database and GeneCards database,OMIM database,ClinVar database and Varsome database.Results A male patient,an age of 7 months and 25 days,who had generalized tonic-myoclonic seizures(GTCS)and global developmental delay(GDD)since six months old.The denovo nonsense mutation in the MBD5 gene detected by trioWES,NM_018328:c.440C>A/p.S147*,is a recurrent variant found in multiple patients(rs886041003).The phenotype of this case is similar to the previously reported S147*case and highly consistent with the phenotype of the case with T157Qfs4 located downstream of the C-terminus of the same protein chain region(AA123-152).Conclusions Finding of MBD5 S147*in this case enriches the associated phenotype of this recurrent variant.Compared with clinical features with previously reported MRD1 cases,finding in this study indicates that MBD5 protein region AA123-152 may have some potential unknown functions related to the MRD1 phenotype,which needs to be further explored.

关 键 词：MDB5 常染色体显性遗传性智力障碍 外显子组测序 热点变异 婴儿期早期诊断 

分 类 号：R742.1[医药卫生—神经病学与精神病学]