16p11.2微缺失综合征伴发Rett综合征1例患儿的临床及分子遗传学分析

Clinical and molecular genetic analysis of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome

目的探讨l例16p11.2微缺失综合征伴发Rett综合征(RTT)患儿的遗传学特征。方法以2020年5月就诊于甘肃省妇幼保健院的1例男性患儿作为研究对象,收集其临床资料。采集患儿及其父母的外周血样,提取基因组DNA,进行家系全外显子组测序(WES),并用Sanger测序对候选变异进行验证。结果患儿为出生4 d的男婴,表现为反应差、纳差、喂养困难,于8个月时死亡。WES测序提示其染色体16p11.2区缺失约0.643 Mb,该区域包含16p11.2微缺失综合征的关键基因ALDOA、CORO1A、KIFF22、PRRT2和TBX6等,患儿父亲携带相同区域的缺失,判断为致病性拷贝数变异。患儿MECP2基因存在母源性c.763C>T(p.R255X)半合子变异,为致病性变异(PVS1+PS4+PM2_Supporting)。结论染色体16p11.2区域的缺失以及MECP2:c.763C>T(p.R255X)变异考虑是该患儿的遗传学病因。

Objective To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome(RTT).Methods A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject.Clinical data of the infant was collected.Genomic DNA was extracted from peripheral blood samples from the infant and his parents,and subjected to whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing.ResultThe patient,a 4-day-old male infant,had presented with poor response,poor intake,feeding difficulties,and deceased at 8 months after birth.WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region,which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA,CORO1A,KIFF22,PRRT2 and TBX6.His father has carried the same deletion,but was phenotypically normal.The deletion was predicted to be pathogenic.The child was also found to harbor a maternally derived c.763C>T(p.R255X)hemizygous variant of the MECP2 gene,which was also predicted to be pathogenic(PVS1+PS4+PM2_Supporting).Conclusion The 16p11.2 deletion and the MECP2:c.763C>T(p.R255X)variant probably underlay the pathogenesis in this infant.