Extensive molecular analysis of patients bearing CFTR-related disorders.

6533b7d4fe1ef96bd1263247

RESEARCH PRODUCT

Extensive molecular analysis of patients bearing CFTR-related disorders.

Marcello Ciaccio Chiara Bellia Giuseppe Castaldo Giuseppe Cardillo Felice Amato Ausilia Elce Rossella Tomaiuolo Francesca Lembo

subject

Epithelial sodium channel congenital hereditary and neonatal diseases and abnormalities Cystic fibrosis CFTR SLC26A SCNN Cystic Fibrosis Anion Transport Proteins DNA Mutational Analysis molecular analysi Cystic Fibrosis Transmembrane Conductance Regulator Gene mutation Pathology and Forensic Medicine congenital bilateral absence of vasa deferentes Exon Gene Frequency disseminated bronchiectasis congenital bilateral absence of vasa deferente Humans Trypsin molecular analysis Epithelial Sodium Channels Gene Cells Cultured Genetic Association Studies Genetics biology disseminated bronchiectasi Epithelial Cells respiratory system recurrent pancreatiti digestive system diseases Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Solute carrier family CFTR related disorders Trypsin Inhibitor Kazal Pancreatic Case-Control Studies RNA splicing Mutation biology.protein Molecular Medicine CFTR related disorder SLC26 family Carrier Proteins Na channel ENaC Minigene recurrent pancreatitis

description

Cystic fibrosis transmembrane conductance regulator (CFTR)–related disorders (CFTR-RDs) may present with pancreatic sufficiency, normal sweat test results, and better outcome. The detection rate of mutations is lower in CFTR-RD than in classic CF: mutations may be located in genes encoding proteins that interact with CFTR or support channel activity. We tested the whole CFTR coding regions in 99 CFTR-RD patients, looking for gene mutations in solute carrier (SLC) 26A and in epithelial Na channel (ENaC) in 33 patients who had unidentified mutations. CFTR analysis revealed 28 mutations, some of which are rare. Of these mutations, RT-PCR demonstrated that the novel 1525-1delG impairs exon 10 splicing; by using minigene analysis, we excluded the splicing effect of three other novel intronic variants. Analysis of SLC26A genes revealed several variants, some of which are novel, that did not affect mRNA expression. Other mutations occurred in the ENaC genes encoding the ENaC subunits, but their frequency did not significantly differ between patients and controls. Our data, although obtained on a preliminary cohort of CFTR-RD patients, exclude a role of mutations in SLC26A and in SCNN genes in the pathogenesis of such disease; we confirm that CFTR analysis has a relevant role in CFTR-RD patients; and it appears mandatory to use CFTR scanning techniques and approaches to reveal the effect of novel mutations.

year	journal	country	edition	language
2012-01-01

10.1016/j.jmoldx.2011.09.001 http://hdl.handle.net/11588/458058