Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations
- Georgios Loudianosa,
- Valeria Dessib,
- Mario Lovicuc,
- Andrea Angiusd,
- Buket Altuntase,
- Raffaella Giacchinof,
- Maria Marazzig,
- Matilde Marcellinih,
- Maria Rita Sartorellih,
- Giacomo Carlo Sturnioloi,
- Nurten Kocakj,
- Aysel Yucej,
- Nejat Akark,
- Mario Pirastud,
- Antonio Caoa,b,c
- aOspedale Regionale per Le Microcitemie ASL 8, Via Jenner s/n, 09100 Cagliari, Italy, bIstituto di Clinica e Biologia dell’Età Evolutiva, Università degli Studi di Cagliari, Italy, cIstituto di Ricerca sulle Talassemie ed Anemie Mediterranee, CNR, Cagliari, Italy, dIstituto di Genetica Molecolare, CNR, Alghero, Italy, eDepartment of Paediatric Gastroenterology, Gazi University, Ankara, Turkey, fDivisione Malattie Infettive, Istituto Gaslini, Genova, Italy, gClinica di Malattie Infettive, Istituto Gaslini, Genova, Italy, hOspedale Pediatrico Bambin Gesu, Roma, Italy, iGastroenterologia, Padova, Italy, jGastroenterology Unit, Hacettepe University, Ankara, Turkey, kPaediatric Molecular Biology Ankara University, Turkey
- Dr Loudianos.
- Revised 18 May 1999
- Accepted 7 June 1999
Abstract
In this study, we report further results of mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Mediterranean origin. A total of 136 WD chromosomes, 73 of which were of Italian, 43 of Turkish, 18 of Sardinian, and two of Spanish origin, were analysed and the mutation characterised in 84.5% of them. We found 50 different mutations of which 19 are novel, including three nonsense, one frameshift, and 15 missense mutations. The mutations detected were rare and mostly found in the compound heterozygous state together with other mutations and only rarely in homozygosity. Most of these mutations lie in the transmembrane and ATP binding loop regions. These data expand our knowledge of both the structure-function relationships of the WD protein and the molecular pathology of WD, thus improving our capability of prevention and genetic counselling.
