Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis.

摘要: Cystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations characterized detail by CFTR2 database, which complicates its analysis conventional methods. We conducted next-generation sequencing (NGS) a cohort 89 adult patients negative for p.Phe508del homozygosity. Complete clinical demographic information were available 84 patients. By combining MLPA NGS, we identified alleles all CF Importantly, 10% cases, standard bioinformatics pipelines inefficient identifying causative mutations. Class IV-V observed 38 (45%) predominantly ones pancreatic sufficient disease; rest had I-III Diabetes was seen only homozygous class found that 12% heterozygous more than two Two p.[Arg1070Gln, Ser466*] complex allele associated milder pulmonary obstructions (FVC 107 109% versus 67%, CI 95%: 63-72%; FEV 90 111% 47%, 37-48%). For first time p.[Phe508del, Leu467Phe] reported, four (5%). NGS can information-gaining technology compared Combined equivalent diagnostic performance, it therefore implemented practice, although careful validation still required.