caa a22 4500 397574134 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199603 xx s 000 0 eng 10.1093/hmg/5.3.351 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.3.351 Endothelin-B Receptor Mutations in Patients with Isolated Hirschsprung Disease from a Non-Inbred Population [Elektronische Daten] [Alberto Auricchio, Giorgio Casari, Annamaria Staiano, Andrea Ballabio] Hirschsprung disease (HSCR), or aganglionic megacolon, is the most common cause of congenital intestinal obstruction. Two different loci have been found to be tightly linked to HSCR on chromosomes 10 and 13, respectively. Recently, mutations in the RET protooncogene on chromosome 10q11.2 were identified in several HSCR patients. In addition, a missense mutation in the endothelin-B receptor (EDNRB) gene on chromosome 13q22 was found in an inbred Mennonite kindred affected by HSCR and associated abnormalities, demonstrating the involvement of EDNRB in HSCR pathogenesis. To test whether mutations in the EDNRB gene could account for Hirschsprung in patients from non-inbred populations, we analysed DNA samples from 17 probands of Italian origin with HSCR. We have identified two novel EDNRB mutations: a missense mutation in a sporadic case, S305N, which leads to a change of a serine to an asparagine, disrupting a putative phosphorylation site; and a single nucleotide deletion in a familial case, N378I, resulting in a truncated protein. Both mutations were found in one of the healthy parents, and neither of these mutations were found in any of the normal individuals tested. These data confirm the involvement of EDNRB in HSCR pathogenesis and demonstrate that EDNRB mutations could contribute to HSCR disease in non-inbred populations. © 1996 Oxford University Press Auricchio Alberto Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut Casari Giorgio Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut Staiano Annamaria Department of Pediatrics, ‘Federico II' University, Via Pansini 5, 80131 Naples, Italy aut Ballabio Andrea Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut Human Molecular Genetics Oxford University Press 5/3(1996-03), 351-354 0964-6906 5:3<351 1996 5 hmg https://doi.org/10.1093/hmg/5.3.351 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.3.351 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Auricchio Alberto Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut NATIONALLICENCE 700 1- Casari Giorgio Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut NATIONALLICENCE 700 1- Staiano Annamaria Department of Pediatrics, ‘Federico II' University, Via Pansini 5, 80131 Naples, Italy aut NATIONALLICENCE 700 1- Ballabio Andrea Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/3(1996-03), 351-354 0964-6906 5:3<351 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