Analysis of MCCC2 gene variant in a pedigree affected with 3-methylcrotonyl coenzyme A carboxylase deficiency.
10.3760/cma.j.cn511374-20200110-00021
- Author:
Rui LI
1
;
Zhaojie XU
;
Ding ZHAO
;
Yaodong ZHANG
;
Zhenhua XIE
;
Chaojie WANG
;
Zhenhua ZHANG
;
Jijun SONG
Author Information
1. Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450018, China. xuzhaojie01@126.com.
- Publication Type:Journal Article
- MeSH:
Carbon-Carbon Ligases/genetics*;
Child;
Female;
Humans;
Male;
Mutation, Missense/genetics*;
Pedigree;
Urea Cycle Disorders, Inborn/genetics*
- From:
Chinese Journal of Medical Genetics
2021;38(1):74-77
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a child with clinically suspected 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD).
METHODS:Genomic DNA was extracted from peripheral blood samples of the proband and her parents. Whole exome sequencing was used to screen pathogenic variant in the proband. Suspected variant was verified by Sanger sequencing. Impact of the variant on the structure and function of protein product was analyzed by using bioinformatic software.
RESULTS:Sanger sequencing showed that the proband has carried homozygous missense c.1342G>A (p.Gly448Ala) variant of the MCCC2 gene, for which her mother was a heterozygous carrier. The same variant was not detected in her father. The variant was predicted to be pathogenic by PolyPhen-2 and Mutation Taster software, and the site was highly conserved among various species. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.1342G>A (p.Gly448Ala) variant of MCCC2 gene was predicted to be likely pathogenic(PM2+PP2-PP5).
CONCLUSION:The homozygous missense variant of the MCCC2 gene c.1342G>A (p.Gly448Ala) probably underlay the molecular pathogenesis of the proband. Genetic testing has confirmed the clinical diagnosis.
