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Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients

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...

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Autores principales: Alanazi, Mohammed, Al-Arfaj, Abdulrahman Saud, Abduljaleel, Zainularifeen, Fahad Al-Arfaj, Hussein, Reddy Parine, Narasimha, Purusottapatnam Shaik, Jilani, Khan, Zahid, Ali Khan Pathan, Akbar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119946/
https://www.ncbi.nlm.nih.gov/pubmed/25136576
http://dx.doi.org/10.1155/2014/290325
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author Alanazi, Mohammed
Al-Arfaj, Abdulrahman Saud
Abduljaleel, Zainularifeen
Fahad Al-Arfaj, Hussein
Reddy Parine, Narasimha
Purusottapatnam Shaik, Jilani
Khan, Zahid
Ali Khan Pathan, Akbar
author_facet Alanazi, Mohammed
Al-Arfaj, Abdulrahman Saud
Abduljaleel, Zainularifeen
Fahad Al-Arfaj, Hussein
Reddy Parine, Narasimha
Purusottapatnam Shaik, Jilani
Khan, Zahid
Ali Khan Pathan, Akbar
author_sort Alanazi, Mohammed
collection PubMed
description 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.
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spelling pubmed-41199462014-08-18 Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients Alanazi, Mohammed Al-Arfaj, Abdulrahman Saud Abduljaleel, Zainularifeen Fahad Al-Arfaj, Hussein Reddy Parine, Narasimha Purusottapatnam Shaik, Jilani Khan, Zahid Ali Khan Pathan, Akbar Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2014 2014-07-09 /pmc/articles/PMC4119946/ /pubmed/25136576 http://dx.doi.org/10.1155/2014/290325 Text en Copyright © 2014 Mohammed Alanazi et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Alanazi, Mohammed
Al-Arfaj, Abdulrahman Saud
Abduljaleel, Zainularifeen
Fahad Al-Arfaj, Hussein
Reddy Parine, Narasimha
Purusottapatnam Shaik, Jilani
Khan, Zahid
Ali Khan Pathan, Akbar
Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title_full Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title_fullStr Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title_full_unstemmed Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title_short Novel Hypoxanthine Guanine Phosphoribosyltransferase Gene Mutations in Saudi Arabian Hyperuricemia Patients
title_sort novel hypoxanthine guanine phosphoribosyltransferase gene mutations in saudi arabian hyperuricemia patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119946/
https://www.ncbi.nlm.nih.gov/pubmed/25136576
http://dx.doi.org/10.1155/2014/290325
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