High heterogeneity for cystic fibrosis in Spanish families: 75 mutations account for 90% of chromosomes |
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Authors: | Teresa Casals Maria D Ramos Javier Giménez Sara Larriba Virginia Nunes X Estivill |
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Institution: | (1) Medical and Molecular Genetics Center – IRO, Hospital Duran i Reynals, Avia. Castelldefels, Km. 2.7, L’Hospitalet de Llobregat, E-08 907 Barcelona, Catalonia, Spain Tel.: +343 263 0039; Fax: +343 263 2251; e-mail: estivill@iro.es, ES |
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Abstract: | We have analyzed 640 Spanish cystic fibrosis (CF) families for mutations in the CFTR gene by direct mutation analysis, microsatellite haplotypes, denaturing gradient gel electrophoresis, single-strand conformation
analysis and direct sequencing. Seventy-five mutations account for 90.2% of CF chromosomes. Among these we have detected seven
novel CFTR mutations, including four missense (G85V, T582R, R851L and F1074L), two nonsense (E692X and Q1281X) and one splice site mutation
(711+3A→T). Three variants, two in intronic regions (406-112A/T and 3850-129T/C) and one in the coding region (741C/T) were
also identified. Mutations G85V, T582R, R851L, E692X and Q1281X are severe, with lung and pancreatic involvement; 711+3A→T
could be responsible for a pancreatic sufficiency/insufficiency variable phenotype; and F1074L was associated with a mild
phenotype. These data demonstrate the highest molecular heterogeneity reported so far in CF, indicating that a wide mutation
screening is necessary to characterize 90% of the Spanish CF alleles.
Received: 3 July 1997 / Accepted: 20 August 1997 |
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