Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis‐like phenotypes. (28th July 2013)

• Record Type: Journal Article
• Authors: Ramos, M.D.; Trujillano, D.; Olivar, R.; Sotillo, F.; Ossowski, S.; Manzanares, J.; Costa, J.; Gartner, S.; Oliva, C.; Quintana, E.; Gonzalez, M.I.; Vazquez, C.; Estivill, X.; Casals, T.
• Is Part Of: Clinical genetics. Volume 86:Number 1(2014:Jul.)
• Page Start: 91
• Page End: 95
• Publication Date: 2013-07-28
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12234
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12234-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12234-para-0001">The term cystic fibrosis (CF)‐like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two <italic>CFTR</italic>(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (<italic>SCNN1A</italic>, <italic>SCNN1B</italic>, <italic>SCNN1G</italic> and <italic>SERPINA1</italic>) in a cohort of 10 uncharacterized patients with CF and CF‐like disease. We have used whole‐exome sequencing to characterize mutations in the <italic>CFTR</italic> gene and these four candidate genes. <italic>CFTR</italic> molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in <italic>SCNN1A</italic>, <italic>SCNN1B</italic>, <italic>SCNN1G</italic> and <italic>SERPINA1</italic> in six patients with CF‐like phenotypes were confirmed by Sanger sequencing and were further supported by <italic>in silico</italic> predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF‐like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors.</p> </abstract>