caa a22 4500 397574231 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/hmg/5.2.293 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.2.293 Localisation of Pseudohypoaldosteronism Genes to Chromosome 16p12.2-13.11 and 12p13.1-Pter by Homozygosity Mapping [Elektronische Daten] [Sandra S. Strautnieks, Richard J. Thompson, Aaron Hanukoglu, Michael J. Dillon, Israel Hanukoglu, Ursula Kuhnle, Jonathan Seckl, R. Mark Gardiner, Eddie Chung] Pseudohypoaldosteronism type 1 (PHA1, OMIM 264350) is a rare Mendelian disorder characterised by end-organ unresponsiveness to mineralocorticoids. Most steroid hormone insensitivity syndromes arise from mutations in the corresponding receptor, but available genetic evidence is against involvement of the mineralocorticoid receptor gene, MLR, in PHA1. A complete genome scan for PHA1 genes was undertaken using homozygosity mapping in 11 consanguineous families. Conclusive evidence of linkage with heterogeneity was obtained with a maximum two-locus admixture lod score of 9.9. The disease locus mapped to chromosome 16p12.2-13.11 in six families and to 12p13.1-pter in the other five families. The two chromosomal regions harbour genes for subunits of the amiloride-sensitive epithelial sodium channel: SCNN1B and SCNN1G on 16p and SCNN1A on 12p. Liddle's syndrome of hypertension and pseudoaldos-teronism has been shown to arise from mutations in SCNN1B and SCNN1G These results strongly suggest that PHA1 and Liddle's syndrome are allelic variants caused by mutations in genes encoding subunits of this sodium channel. These genes are of broad biological interest both in relation to sodium and water homeostasis in mammals and by virtue of their homology to the mec genes of Caenorhabditis elegans involved in mechanosensitivity and neuronal degeneration. © 1996 Oxford University Press Strautnieks Sandra S. Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut Thompson Richard J. Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut Hanukoglu Aaron Department of Paediatrics, E. Wolfson Hospital, and Tel-Aviv University, Sackler School of Medicine, Tel-Aviv, Israel aut Dillon Michael J. Division of Medicine, Institute of Child Health and Renal Unit, Great Ormond Street Hospital for Children NHS Trust, 30 Guilford Street, London WC1N 1EH, UK aut Hanukoglu Israel Research Institute, College of Judea and Samaria, Ariel 44820, and Institute of Endocrinology, Sourasky Medical Centre, Tel-Aviv, Israel aut Kuhnle Ursula University of Munich, Children's Hospital, D-80337 Munich, Germany aut Seckl Jonathan Department of Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, Scotland EH4 2XU, UK aut Gardiner R. Mark Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut Chung Eddie Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut Human Molecular Genetics Oxford University Press 5/2(1996-02), 293-299 0964-6906 5:2<293 1996 5 hmg https://doi.org/10.1093/hmg/5.2.293 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.2.293 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Strautnieks Sandra S. Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut NATIONALLICENCE 700 1- Thompson Richard J. Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut NATIONALLICENCE 700 1- Hanukoglu Aaron Department of Paediatrics, E. Wolfson Hospital, and Tel-Aviv University, Sackler School of Medicine, Tel-Aviv, Israel aut NATIONALLICENCE 700 1- Dillon Michael J. Division of Medicine, Institute of Child Health and Renal Unit, Great Ormond Street Hospital for Children NHS Trust, 30 Guilford Street, London WC1N 1EH, UK aut NATIONALLICENCE 700 1- Hanukoglu Israel Research Institute, College of Judea and Samaria, Ariel 44820, and Institute of Endocrinology, Sourasky Medical Centre, Tel-Aviv, Israel aut NATIONALLICENCE 700 1- Kuhnle Ursula University of Munich, Children's Hospital, D-80337 Munich, Germany aut NATIONALLICENCE 700 1- Seckl Jonathan Department of Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, Scotland EH4 2XU, UK aut NATIONALLICENCE 700 1- Gardiner R. Mark Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut NATIONALLICENCE 700 1- Chung Eddie Department of Paediatrics, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/2(1996-02), 293-299 0964-6906 5:2<293 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford