Prenatal molecular diagnosis of glutaric aciduria type I by direct mutation analysis

Various biochemical strategies are followed for the prenatal diagnosis of glutaric aciduria type I (GA I). However, since the description of patients with normal excretion of glutarate and significant residual activity, the difficulties of prenatal biochemical diagnosis are obvious. The characterization of the glutaryl-CoA dehydrogenase (GCDH) gene has allowed us to develop a single strand conformation polymorphism (SSCP) screening method, followed by direct sequencing, to identify the disease causing mutations in patients with GA I. Here we report the first prenatal diagnoses based on DNA analysis in chorionic villi biopsy or cultured amniotic fluid cells in three families at risk for GA I. Our results show that this strategy provides a fast and reliable method for prenatal diagnosis. In addition we report two new mutations (1209-1210ins G and R161W) in the GCDH gene that occurred at hypermutable loci.