Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes

Abstract Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in...

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Autores principales:	Do Hyeon Cha, Heon Yung Gee, Raul Cachau, Jong Mun Choi, Daeui Park, Sun Ha Jee, Seungho Ryu, Kyeong Kyu Kim, Hong-Hee Won, Sophie Limou, Woojae Myung, Cheryl A. Winkler, Sung Kweon Cho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/439031d527bb4924b5f4d7dc8ff62cb2
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spelling	oai:doaj.org-article:439031d527bb4924b5f4d7dc8ff62cb22021-12-02T15:08:58ZContribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes10.1038/s41598-019-50798-62045-2322https://doaj.org/article/439031d527bb4924b5f4d7dc8ff62cb22019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50798-6https://doaj.org/toc/2045-2322Abstract Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258 and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.Do Hyeon ChaHeon Yung GeeRaul CachauJong Mun ChoiDaeui ParkSun Ha JeeSeungho RyuKyeong Kyu KimHong-Hee WonSophie LimouWoojae MyungCheryl A. WinklerSung Kweon ChoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Do Hyeon Cha Heon Yung Gee Raul Cachau Jong Mun Choi Daeui Park Sun Ha Jee Seungho Ryu Kyeong Kyu Kim Hong-Hee Won Sophie Limou Woojae Myung Cheryl A. Winkler Sung Kweon Cho Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
description	Abstract Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258 and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.
format	article
author	Do Hyeon Cha Heon Yung Gee Raul Cachau Jong Mun Choi Daeui Park Sun Ha Jee Seungho Ryu Kyeong Kyu Kim Hong-Hee Won Sophie Limou Woojae Myung Cheryl A. Winkler Sung Kweon Cho
author_facet	Do Hyeon Cha Heon Yung Gee Raul Cachau Jong Mun Choi Daeui Park Sun Ha Jee Seungho Ryu Kyeong Kyu Kim Hong-Hee Won Sophie Limou Woojae Myung Cheryl A. Winkler Sung Kweon Cho
author_sort	Do Hyeon Cha
title	Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
title_short	Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
title_full	Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
title_fullStr	Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
title_full_unstemmed	Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
title_sort	contribution of slc22a12 on hypouricemia and its clinical significance for screening purposes
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/439031d527bb4924b5f4d7dc8ff62cb2
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Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes

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