Differential diagnosis of a Chinese pedigree with methylmalonic acidemia by next-generation sequencing
10.3760/cma.j.cn511374-20210518-00425
- VernacularTitle:一个甲基丙二酸血症家系的高通量测序鉴别诊断
- Author:
Ganye ZHAO
1
;
Chen CHEN
;
Xuechao ZHAO
;
Lina LIU
;
Conghui WANG
;
Xiangdong KONG
Author Information
1. 郑州大学第一附属医院妇产医学部遗传与产前诊断中心，郑州 450052
- Keywords:
Next-generation sequencing;
Methylmalonic acidemia;
Propionic acidemia;
Genetic testing
- From:
Chinese Journal of Medical Genetics
2022;39(7):694-697
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of a child with suspected propionic acidemia.Methods:Genomic DNA was extracted from peripheral blood sample of the child and subjected to high-throughput sequencing to screen pathogenic variants of genes associated with methylmalonic acidemia and propionic acidemia, including MUT, MMACHC, MMAA, MMAB, MMADHC, LMBRD1, PCCA, PCCB and SLC22A5. Candidate variants were verified by Sanger sequencing of the proband, her parents and sister. Results:The proband was found to harbor two pathogenic variants of the MUT gene, namely c. 1560+ 2T>C and c. 729_730insTT (p.Asp244fs), but not in genes associated with propionic acidemia. Her sister and father had carried c. 1560+ 2T>C, and her mother had carried c. 729_730insTT (p.Asp244fs). Conclusion:The proband was diagnosed as methylmalonic acidemia due to compound heterozygous variants of c. 1560+ 2T>C and c. 729_730insTT (p.Asp244fs) of the MUT gene. Her elder sister and parents were all carriers. Genetic testing has facilitated differential diagnosis of methylmalonic acidemia and propionic acidemia in this pedigree.
