R58fs Mutation in HGO Gene in a Family with Alkaptonuria in the UAE

摘要

This study was conducted to determine the prevalence of alkaptonuria in the UAE population and to identify the genotype of affected individuals. Urine collected from 2857 school pupils was analysed for homogentisic acid by gas chromatography-mass spectrometry. Genomic DNA was isolated from the white blood cells of all family members of the affected case following standard established protocols. PCR using specific primers to amplify HGO gene 14 exons with the flanking intronic sequences including the splice sites sequences were designed. One sample was highly positive for homogentisic acid. In this family one other member, a 22 year old brother, was found to excrete HGA. Another, a sister who had not provided a urine sample, was discovered by genetic testing. We found a single nucleotide deletion c342 del A, located in exon 3 and which resulted in a frameshift at amino acid position 58 (R58fs). Alkaptonuria may be more common than is thought to be with an allele prevalence estimated at 0.0107 (95% CI 0.000392 - 0.03473).