Clinical and variation analysis of three Chinese families affected with glutaric acidemia type 1.
10.3760/cma.j.issn.1003-9406.2018.06.004
- Author:
Xiaorong SHI
1
;
Zhonglin KE
;
Aidong ZHENG
;
Wenhuang XIE
;
Guiling MO
Author Information
1. Department of Pediatrics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China. shixiaorong1@163.com.
- Publication Type:Journal Article
- MeSH:
Amino Acid Metabolism, Inborn Errors;
diagnosis;
genetics;
Brain Diseases, Metabolic;
diagnosis;
genetics;
China;
DNA Mutational Analysis;
Glutaryl-CoA Dehydrogenase;
deficiency;
genetics;
Humans;
Mutation
- From:
Chinese Journal of Medical Genetics
2018;35(6):796-799
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To detect potential variation in glutaryl-CoA dehydrogenase (GCDH) gene among three Chinese families affected with glutaric acidemia type Ⅰ(GA-1) and correlate the genotypes with phenotypes.
METHODS:Genomic DNA was extracted from peripheral blood samples derived from three patients with GA-1 and their family members. The coding regions of the GCDH gene were amplified with PCR and subjected to Sanger sequencing.
RESULTS:The clinical manifestation of the patients varied from macrocephaly to severe encephalopathy, with notable phenotypic difference between siblings carrying the same variation. In pedigrees 1 and 2, the probands have carried compound heterozygous variations c.1133C>T(p.Ala378Val) and c.1244-2A>C, which were derived their fathers and mothers, respectively. In pedigree 3, the proband has carried compound heterozygous variation c.339delT (p.Tyr113) and c.406G>T (p.Gly136Cys). Among these, variations c.339delT and c.1133C>T were verified as novel by retrieval of dsSNP, HGMD and 1000 genome database. Bioinformatic analysis suggested that above variations can affect protein function and are probably pathogenic.
CONCLUSION:Above discovery has expanded the mutation spectrum of the GCDH gene. No correlation was found between the clinical phenotype and genotype of GA-1 patients.
