title: Novel hypoxanthine guanine phosphoribosyltransferase gene mutations in Saudi Arabian hyperuricemia patients.
abstract: Over the past decade, a steady increase in the incidence of HPRT-related hyperuricemia (HRH) has been observed in Saudi Arabia. We examined all the nine exons of HPRT gene for mutations in ten biochemically confirmed hyperuricemia patients, including one female and three normal controls. In all, we identified 13 novel mutations in Saudi Arabian HPRT-related hyperuricemia patients manifesting different levels of uric acid. The Lys103Met alteration was highly recurrent and was observed in 50% of the cases, while Ala160Thr and Lys158Asn substitutions were found in two patients. Moreover, in 70% of the patients ≥2 mutations were detected concurrently in the HPRT gene. Interestingly, one of the patients that harbored Lys103Met substitution along with two frameshift mutations at codons 85 and 160 resulting in shortened protein demonstrated unusually high serum uric acid level of 738 μmol/L. Two of the seven point mutations that resulted in amino acid change (Lys103Met and Val160Gly) were predicted to be damaging by SIFT and Polyphen and were further analyzed for their protein stability and function by molecular dynamics simulation. The identified novel mutations in the HPRT gene may prove useful in the prenatal diagnosis and genetic counseling.
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alanazi
authors.affiliation: Department of Medicine, King Saud University Hospital, Riyadh 11426, Saudi Arabia.
authors.forename: Abdulrahman Saud
authors.initials: AS
authors.lastname: Al-Arfaj
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
authors.forename: Zainularifeen
authors.initials: Z
authors.lastname: Abduljaleel
authors.affiliation: Department of Medicine, King Saud University Hospital, Riyadh 11426, Saudi Arabia.
authors.forename: Hussein
authors.initials: H
authors.lastname: Fahad Al-Arfaj
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Narasimha
authors.initials: N
authors.lastname: Reddy Parine
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Jilani
authors.initials: J
authors.lastname: Purusottapatnam Shaik
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ali Khan Pathan
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012529:Saudi Arabia; D014527:Uric Acid / Q000097:blood
chemical_list: D014527:Uric Acid; D007041:Hypoxanthine Phosphoribosyltransferase