10 Mild cystic fibrosis phenotype in adult patients with novel 3272–16T>A mutation

Abstract

Objective Patients who have milder symptoms or atypical cystic fibrosis (CF) may have at least one so called class V mutation. This class includes mutations that leave residual levels of normal CFTR transcripts and protein. Recently by sequencing of the coding region of the CFTR gene and exon-intron junctions we've revealed 3272–16T>A mutation in Russian adult CF patients. As far as we know this mutation hasn't been described (before December 2014) by any other geneticists and it is not in the CFTR1 and CFTR2 lists. 3272–16T>A mutation is a splicing mutation in intron 19 of CFTR gene (thymine to adenine substitution). Aim To reveal the clinical characteristics of 3272–16T>A mutation in CF adult patients. Methods Adult CF patients carrying 3272–16T>A mutation were included in the study. The following data were evaluated: the age at CF diagnosis, pancreatic status, the presence of the following complications: meconium ileus or DIOS, diabetes and liver cirrhosis. Results We've found 10 patients (6 men) carried 3272–16T>A mutation and the following mutations in the other CFTR allele: F508del – 6 patients, 394delTT – 2 patients, 2184insA – 1 patient, not identified – 1 patient. The average age of patients was 27.4±5.5 years (from 18.4 to 35.0 years). Age at diagnosis ranged from 3.5 to 26.9 years (12.3±7.0 yrs). All 10 were pancreatic sufficient. None of them had meconium ileus in anamnesis or DIOS, diabetes and liver cirrhosis. Conclusion 3272–16T>A mutation is a mild mutation associated with pancreatic sufficiency and lack of development of some complications specific to the classical CF genotypes.