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

Abstract

SummaryThis study was conducted to determine the prevalence of alkaptonuria in the UAE population and to identify the genotype of affected individuals. In a 3 stage sampling technique 2981 pupils from Government schools in Al Ain and private schools in Dubai were selected to take part in the study, of whom 2857 provided urine samples. Urine collected 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. Specific PRC primers were designed to amplify all 14 exons of the HGD gene with the flanking intronic sequences including the splice site sequences. 2857 children returned a viable urine sample, of which one was highly positive for homogentisic acid. All 12 members of this girl's family were studied and one, 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. There were no complaints of joint pain or other symptoms in any member of this family. Parents were first cousins. We found a single nucleotide deletion c.342delA, located in exon 3, which resulted in a frameshift at amino acid position 58 (p.Arg58fs or p.R58fs). Alkaptonuria may be more common than it is thought to be with an allele prevalence estimated at 0.0107 (95% CI 0.000392 -0.03473) . The R58fs mutation is old, perhaps having occurred several thousand years ago, and has spread over a large geographical area.

Mutation Spectrum and Birth Prevalence of Inborn Errors of Metabolism among Emiratis : A Study from Tawam Hospital Metabolic Center , United Arab Emirates

“…The Centre for Arab Genomic Studies (CAGS) 6,[18][19][20][21] In the case of isovaleric aciduria, three mutations (p.R392H, p.R395Q and p.F382fs) were reported in four unrelated Emirati families and one mutation (p.E408K) in an Egyptian family. 20 Alkaptonuria, due to the single nucleotide deletion of c.342delA (c.174delA), was reported in a family from Al Ain, UAE; the allelic prevalence was estimated at about 1%.…”

“…20 Alkaptonuria, due to the single nucleotide deletion of c.342delA (c.174delA), was reported in a family from Al Ain, UAE; the allelic prevalence was estimated at about 1%. 21 In the UAE, screening began for PKU in 1995, for congenital hypothyroidism in 1998, sickle cell disease in 2002, congenital adrenal hyperplasia in 2005 and biotinidase deficiency in 2010. [22][23][24] The Expanded National Neonatal Screening Programme, implemented in 2011, covers over 90% of all neonates.…”

Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)

“…Abdulrazzaq et al [2009] screened 2,981 school children for homogentisic acid and identified a family with high levels of this metabolite indicating alkaptonuria. Table 9 lists the mutations identified in some metabolic disorders in the UAE.…”

Novel mutations in the homogentisate 1,2 dioxygenase gene identified in Jordanian patients with alkaptonuria

“…Few studies have been conducted to determine the genotype of affected individuals with AKU and mutations in the HGD gene in arab population. Abdulrazzaq et al [18] found a single-nucleotide deletion c.342delA in exon 3 in a family with AKU in the United arab emirates, which resulted in a frameshift at amino acid position 58 (R58fs) [18].…”