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

 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 
 SCIENTIFIC REPORTS, Vol.9(1) : e14360, 2019 
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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.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
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