Molecular Study and Mutational Analysis of Glutaric Aciduria Type I in Egyptian infants

Abstract

Glutaricaciduriatype I (GAI) is an autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase (GCDH).GAI is one of the treatable metabolic disorders characterized by macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy. In this study, the clinical, biochemical and molecular profile of twenty one patients with GAI from twenty one unrelated families from Egypt were carried out. RNA was extracted from whole blood for synthesis of cDNA, the fragment of GCDH was amplified and sequenced.In this study, a total of 15 different mutations were reportedbetween Egyptian families ranging from missense, nonsense, frame shift and silent mutations. A five novel mutations in GCDH gene(c.148T>A (p.Trp50Arg), c.158C>A (p.Pro53Gln), c.1284C>G (p.Ile428Met), c.644_645insCTCG(p.(Pro217Leufs*14) and c.1189G>T (p.Glu397*)) were reported. In addition to seven mutations have been published previously and 3 silent mutations in 3`-UTR region. It is clear that out of 21 patientsExons4 (3 mutations/3 patients), 6 (3 mutations/4 patients),8 (2 mutations/4 patients) and 11(2 mutations/8 patients) are hot spot regions of GCDH gene representing 14%, 20%, 20% and 38% respectively of patients. Molecular confirmation is helpful in providing genetic counseling and prenatal diagnosis in subsequent pregnancy.An early diagnosis and timely intervention can improve the underlying prognosis.