Clinical features and genetic analysis of a child with Central core disease due to compound heterozygous variants of RYR1 gene
10.3760/cma.j.cn511374-20230418-00216
- VernacularTitle: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
- Author:
Shanshan LIU
1
;
Shuting MAO
;
Bai LI
;
Linlin WEI
;
Yufeng LIU
Author Information
1. 郑州大学第一附属医院小儿内科三病区，郑州 450052
- Keywords:
Genetic Diseases, Inborn;
Central core disease;
RYR1 gene;
Genetic variant
- From:
Chinese Journal of Medical Genetics
2024;41(5):581-585
- CountryChina
- Language:Chinese
-
Abstract:
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.
