NHLBI GO-ESP: Family Studies (Atypical Cystic Fibrosis)

The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. Cystic fibrosis (CF) patients without detectable disease-causing mutations in CFTR present a clinical phenotype very similar to, but possibly discrete from, classic CF. We hypothesize that the phenotype of these atypical CF patients is not due only to mutations in the carbonic anhydrase gene CA12 or in the genes encoding the epithelium sodium ion channel ENaC, but is due to mutations in novel genes that have yet to be associated with CF. The goal of this study is to determine the molecular etiology of this atypical CF.]]>
Inclusion criteria are: elevated sweat chloride levels >40mM, pulmonary dysfunction (lung infections, reduced FEV1, or other respiratory symptoms), and lack of detectable disease-causing mutations in CFTR gene. Family members of individuals with these criteria are also included. Exclusion criteria are: mutations in the CA12 gene or ENaC subunit genes which are predicted to be pathogenic.]]>