caa a22 4500 445861347 CHVBK 20180317145444.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s00439-010-0897-1 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0897-1 Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21 [Elektronische Daten] [Sian Piret, Patrick Danoy, Karin Dahan, Anita Reed, Karena Pryce, William Wong, Rosa Torres, Juan Puig, Thomas Müller, Peter Kotanko, Karl Lhotta, Olivier Devuyst, Matthew Brown, Rajesh Thakker] Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1β) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF-1β mutations are found in only ~45% of FJHN probands, indicating the involvement of other genetic loci in ~55% of probands. To identify other FJHN loci, we performed a single nucleotide polymorphism (SNP)-based genome-wide linkage analysis, in six FJHN families in whom UMOD, HNF-1β and REN mutations had been excluded. Parametric linkage analysis using a ‘rare dominant' model established linkage in five of the six FJHN families, with a LOD score >+3, at 0% recombination, between FJHN and SNPs at chromosome 2p22.1-p21. Analysis of individual recombinants in two unrelated affected individuals defined a ~5.5Mbp interval, flanked telomerically by SNP RS372139 and centromerically by RS896986 that contained the locus, designated FJHN3. The interval contains 28 genes, and DNA sequence analysis of the most likely candidate, solute carrier family 8 member 1 (SLC8A1), did not identify any abnormalities in the FJHN3 probands. FJHN3 is likely located within a ~5.5Mbp interval on chromosome 2p22.1-p21, and identifying the genetic abnormality will help to further elucidate mechanisms predisposing to gout and renal failure. Springer-Verlag, 2010 Piret Sian Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut Danoy Patrick The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut Dahan Karin Division of Nephrology, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate, 1200, Brussels, Belgium aut Reed Anita Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut Pryce Karena The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut Wong William Starship Children's Health, Park Road, 1023, Auckland, New Zealand aut Torres Rosa Division of Internal Medicine, La Paz University Hospital, IdiPAZ, Madrid, Spain aut Puig Juan Division of Internal Medicine, La Paz University Hospital, IdiPAZ, Madrid, Spain aut Müller Thomas Department of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria aut Kotanko Peter Renal Research Institute, 10128, New York, NY, USA aut Lhotta Karl Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, 6800, Feldkirch, Austria aut Devuyst Olivier Division of Nephrology, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate, 1200, Brussels, Belgium aut Brown Matthew The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut Thakker Rajesh Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut Human Genetics Springer-Verlag 129/1(2011-01-01), 51-58 0340-6717 129:1<51 2011 129 439 https://doi.org/10.1007/s00439-010-0897-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0897-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Piret Sian Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut NATIONALLICENCE 700 1- Danoy Patrick The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut NATIONALLICENCE 700 1- Dahan Karin Division of Nephrology, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate, 1200, Brussels, Belgium aut NATIONALLICENCE 700 1- Reed Anita Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut NATIONALLICENCE 700 1- Pryce Karena The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut NATIONALLICENCE 700 1- Wong William Starship Children's Health, Park Road, 1023, Auckland, New Zealand aut NATIONALLICENCE 700 1- Torres Rosa Division of Internal Medicine, La Paz University Hospital, IdiPAZ, Madrid, Spain aut NATIONALLICENCE 700 1- Puig Juan Division of Internal Medicine, La Paz University Hospital, IdiPAZ, Madrid, Spain aut NATIONALLICENCE 700 1- Müller Thomas Department of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Kotanko Peter Renal Research Institute, 10128, New York, NY, USA aut NATIONALLICENCE 700 1- Lhotta Karl Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, 6800, Feldkirch, Austria aut NATIONALLICENCE 700 1- Devuyst Olivier Division of Nephrology, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate, 1200, Brussels, Belgium aut NATIONALLICENCE 700 1- Brown Matthew The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, 4102, Woolloongabba, QLD, Australia aut NATIONALLICENCE 700 1- Thakker Rajesh Academic Endocrine Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Headington, OX3 7LJ, Oxford, UK aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/1(2011-01-01), 51-58 0340-6717 129:1<51 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer