Clinical and variation analysis of three Chinese families affected with glutaric acidemia type 1

Objective To detect potential variation in glutaryl-CoA dehydrogenase (GCDH) gene among three Chinese families affected with glutaric acidemia typeⅠ(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 variant. 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 variants 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. Key words: Glutaric acidemia type Ⅰ; GCDH gene; Gene mutation spectrum