Molecular analysis of Cypriot patients with Glutaric aciduria type I: identification of two novel mutations.

Abstract Objectives The purpose of this study was to identify the mutations in the glutaryl-CoA dehydrogenase gene ( GCDH ) in ten Cypriot patients with Glutaric aciduria type I (GAI). Design and methods Molecular analysis of the GCDH gene was performed by direct sequencing of the patients' genomic DNA. In silico tools were applied to predict the effect of the novel variants on the structure and function of the protein. Results All disease alleles were characterized (mutation detection rate 100%). Five missense mutations were identified: c.192G > T (p.Glu64Asp) and c.803G > T (p.Gly268Val), which are novel, and three previously described mutations, c.1123T > C (p.Cys375Arg), c.1204C > T (p.Arg402Trp) and c.1286C > T (p.Thr429Met). Conclusions Two novel mutations, p.Glu64Asp and p.Gly268Val, account for the majority of disease alleles (76.5%) in Cypriot patients with Glutaric aciduria type I. A founder effect for the p.Glu64Asp and the p.Gly268Val can be suggested based on the place of origin of the carriers of these mutations. Identification of the causative mutations of GAI in Cypriot patients will facilitate carrier detection as well as post- and pre-natal diagnosis.