RYR1基因复合杂合变异所致中央轴空病1例患儿的临床特征及遗传学分析  

Clinical features and genetic analysis of a child with Central core disease due to compound heterozygous variants of RYR1 gene

作　　者：刘姗姗 毛舒婷 李白[1] 魏林林[1] 刘玉峰[1] Liu Shanshan;Mao Shuting;Li Bai;Wei Linlin;Liu Yufeng(Third Ward of Pediatrics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院小儿内科三病区,郑州450052

出　　处：《中华医学遗传学杂志》2024年第5期581-585,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨1例中央轴空病(CCD)患儿的临床特征及遗传学病因。方法选取2022年2月就诊于郑州大学第一附属医院儿童血液科的1例CCD患儿作为研究对象,对患儿进行肌肉病理活检,同时进行全外显子组测序,通过Sanger测序对RYR1基因的候选变异进行家系验证,对患儿的临床特征及基因变异特点进行回顾性分析。结果患儿为12岁男性,表现为运动发育迟缓、面肌无力、上睑下垂、鸡胸、脊柱侧弯等,肌肉活检可见中央核肌纤维,且萎缩肌纤维以Ⅰ型为主。全外显子组测序显示患儿携带RYR1基因c.10561G>A(p.G3521S)和c.3448T>C(p.C1150R)复合杂合变异,分别遗传自母亲和父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南,二者均被判定为可能致病性变异(PS4+PM1+PM2_Supporting+PP3;PM1+PM2_Supporting+PM3+PP3)。结论RYR1基因c.10561G>A(p.G3521S)和c.3448T>C(p.C1150R)复合杂合变异可能是该CCD患儿的遗传学病因。Objective To explore the clinical features and genetic etiology of a child with Central core disease(CCD).Methods A child with CCD who was treated at the Children′s Hematology Department of the First Affiliated Hospital of Zhengzhou University in February 2022 was selected as the study subject.Muscle biopsy was performed.Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA.The child was subjected to whole exome sequencing(WES),and candidate variant was verified by Sanger sequencing.Results The child,a 12-year-old boy,had manifested motor retardation,facial weakness,ptosis,pectus carinatum,scoliosis,etc.Muscle biopsy showed that the central nucleus muscle fibers and atrophic muscle fibers were mainly type I.WES revealed that the child has harbored c.10561G>A(p.G3521S)and c.3448T>C(p.C1150R)compound heterozygous variants of the RYR1 gene.Sanger sequencing confirmed that they were inherited from his mother and father,respectively.Based on the guidelines from the American College of Medical Genetics and Genomics,both variants were considered as likely pathogenic(PS4+PM1+PM2_Supporting+PP3;PM1+PM2_Supporting+PM3+PP3).Conclusion By combining his clinical manifestation and results of muscle pathology and genetic testing,the child was diagnosed with CCD,which may be attributed to the c.10561G>A(p.G3521S)and c.3448T>C(p.C1150R)compound heterozygous variants of the RYR1 gene.

关 键 词：遗传性疾病 先天性 中央轴空病 RYR1基因 基因变异 

分 类 号：R725.9[医药卫生—儿科]