目的:探讨1例中枢核心病(CCD)患儿的临床特点及遗传病因。
方法:选择2022年2月在郑州大学第一附属医院儿童血液科就诊的1例CCD患儿作为研究对象。进行肌肉活检。从儿童及其父母收集外周血样本以提取基因组DNA。这个孩子接受了全外显子组测序(WES),候选变异体通过Sanger测序进行验证。
结果:孩子,一个12岁的男孩,表现出运动迟缓,面部无力,上睑下垂,Carinatum,脊柱侧弯,等。肌肉活检显示,中央核肌纤维和萎缩性肌纤维主要是I型。WES显示该孩子有c.10561G>A(pG3521S)和c.3448T>C(p。C1150R)RYR1基因的复合杂合变体。桑格测序证实它们是从他的母亲和父亲那里继承的,分别。根据美国医学遗传学和基因组学学院的指南,两种变异都被认为可能是致病的(PS4+PM1+PM2_支持+PP3;PM1+PM2_支持+PM3+PP3)。
结论:通过结合他的临床表现和肌肉病理和基因检测结果,这个孩子被诊断出患有CCD,这可能归因于c.10561G>A(p.G3521S)和c.3448T>C(p。C1150R)RYR1基因的复合杂合变体。
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).
CONCLUSIONS: 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.