摘要
目的探讨2例中央核肌病(CNM)新生儿的临床及遗传学特征。方法选取2019年4月至2021年11月华中科技大学同济医学院附属武汉儿童医院临床诊断的2例中央核肌病新生儿作为研究对象,收集其临床信息。对患儿及其父母进行染色体核型分析和全外显子组测序(WES),对候选变异进行Sanger测序家系验证。依据美国医学遗传学与基因组学学会(ACMG)变异解读标准与指南对候选变异进行致病性评估。结果患儿1为出生0.5 h龄男性,患儿2为20日龄男性,主要表现为呼吸困难及吞咽困难。WES提示2例患儿均存在MTM1基因变异,经Sanger测序验证,患儿1的变异为c.1261A>G,为半合子。根据ACMG相关指南评级为致病性变异(PVS1+PM2_Supporting+PP3)。患儿2的变异位点为c.342delT,为半合子。根据ACMG相关指南,c.787C>T评级为致病性变异(PVS1+PM2_Supporting+PP3)。结论MTM1基因c.1261A>G及c.342delT可能为上述2例CNM患儿的遗传学病因。
Objective To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy(CNM).Methods Two newborns with CNM diagnosed clinically at Wuhan Children′s Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects,and their clinical data was collected.Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing(WES).Candidate variants were verified by Sanger sequencing.Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).Results Patient 1 was a male neonate,and Patient 2 was a 20-day-old male infant.Both newborns had featured difficulty in breathing and swallowing.WES revealed that both had harbored hemizygous variants of the MTM1 gene,which were verified by Sanger sequencing.Patient 1 harbored a c.1261A>G variant.Based on the ACMG guidelines,it was rated as pathogenic(PVS1+PM2_Supporting+PP3).Patient 2 harbored a c.342delT variant,which was also rated as pathogenic(PVS1+PM2_Supporting+PP3).Conclusion The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.
作者
王劲
王丹
李婷婷
曾凌空
王石
Wang Jin;Wang Dan;Li Tingting;Zeng Lingkong;Wang Shi(Department of Neonatology,Wuhan Children′s Hospital(Wuhan Maternal and Child Health Care Hospital),Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430070,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2024年第7期812-816,共5页
Chinese Journal of Medical Genetics
基金
湖北省儿科联盟医学科研项目(HBPAMR-2021-06)。
