caa a22 4500 397573782 CHVBK 20180308164849.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1813 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1813 Mutations in the Sulfonylurea Receptor Gene Are Associated with Familial Hyperinsulinism in Ashkenazi Jews [Elektronische Daten] [Ann Nestorowicz, Beth Anne Wilson, Kathleen P. Schoor, Hiroshi Inoue, Benjamin Glaser, Heddy Landau, Charles A. Stanley, Paul S. Thornton, John P. Clement, Joseph Bryan, Lydia Aguilar-Bryan, M. Alan Permutt] Familial hyperinsulinism (HI) is a disorder of pancreatic β-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (i) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (ΔF1388) and (ii) a previously described g→a transition at position −9 of the 3′ splice site of intron 32 (designated 3992-9g→a). Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or ΔF1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. Extended haplotype analyses indicated that the ΔF1388 mutation was associated with a single specific haplotype whereas the 3992-9g→a mutation was primarily associated with a single haplotype but also occurred in the context of several other different haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly associated with mutations in the SUR1 gene and provide evidence for the existence of at least two founder HI chromosomes in this population. © 1996 Oxford University Press Nestorowicz Ann Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut Wilson Beth Anne Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut Schoor Kathleen P. Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut Inoue Hiroshi Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut Glaser Benjamin Department of Endocrinology and Metabolism, The Hebrew University, Hadassah Medical School, Jerusalem, Israel aut Landau Heddy Department of Pediatrics, The Hebrew University, Hadassah Medical School, Jerusalem, Israel aut Stanley Charles A. Division of Endocrinology/Diabetes, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut Thornton Paul S. Division of Endocrinology/Diabetes, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut Clement John P. Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut Bryan Joseph Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut Aguilar-Bryan Lydia Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut Permutt M. Alan Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1813-1822 0964-6906 5:11<1813 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1813 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1813 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nestorowicz Ann Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut NATIONALLICENCE 700 1- Wilson Beth Anne Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut NATIONALLICENCE 700 1- Schoor Kathleen P. Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut NATIONALLICENCE 700 1- Inoue Hiroshi Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut NATIONALLICENCE 700 1- Glaser Benjamin Department of Endocrinology and Metabolism, The Hebrew University, Hadassah Medical School, Jerusalem, Israel aut NATIONALLICENCE 700 1- Landau Heddy Department of Pediatrics, The Hebrew University, Hadassah Medical School, Jerusalem, Israel aut NATIONALLICENCE 700 1- Stanley Charles A. Division of Endocrinology/Diabetes, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut NATIONALLICENCE 700 1- Thornton Paul S. Division of Endocrinology/Diabetes, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut NATIONALLICENCE 700 1- Clement John P. Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Bryan Joseph Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Aguilar-Bryan Lydia Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Permutt M. Alan Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Box 8127, 660 South Euclid Ave., St Louis, MO 63110, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1813-1822 0964-6906 5:11<1813 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