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

Abstract

This study was conducted to identify mutations in the homogentisate 1,2 dioxygenase gene (HGD) in alkaptonuria patients among Jordanian population. Blood samples were collected from four alkaptonuria patients, four carriers, and two healthy volunteers. DNA was isolated from peripheral blood. All 14 exons of the HGD gene were amplified using the polymerase chain reaction (PCR) technique. The PCR products were then purified and analyzed by sequencing. Five mutations were identified in our samples. Four of them were novel C1273A, T1046G, 551-552insG, T533G and had not been previously reported, and one mutation T847C has been described before. The types of mutations identified were two missense mutations, one splice site mutation, one frameshift mutation, and one polymorphism. We present the first molecular study of the HGD gene in Jordanian alkaptonuria patients. This study provides valuable information about the molecular basis of alkaptonuria in Jordanian population.

First Report of a Deletion Encompassing an Entire Exon in the Homogentisate 1,2-Dioxygenase Gene Causing Alkaptonuria

“…The report of this novel mutation in the HGD gene suggests that it could have either recently arisen and did not spread throughout the region or that it may be common but mutation screening of the HGD gene in AKU has not yet been extensively carried out in this area. The identification of novel AKU mutations in Jordan [12] along with this novel 649 bp deletion suggests that AKU in the Middle East may have independent origins than in other parts of the world. Thus, screening for the 649 bp deletion and other mutations in nearby populations would shed further light on the emergence of HGD in this part of the world.…”

A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria

“…Although, a higher birth prevalence of 1 in every 19,000 people was yet observed in Slovakia and the Dominican Republic. However, recently, an increased prevalence was discovered in Jordan and India [17][18][19][20][21][22][23] . AKU is a progressive debilitating disorder for which unfortunately until now only palliative therapies and arthroplasty exist 3,6,10 .…”