Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South Asians

Abstract Background Cystic Fibrosis (CF) genotypes in South Asians are variable with a decreased incidence of Delta F508 and an increased incidence of novel mutations. The objective of this study is to provide clinical evidence that V456A, a novel mutation in South Asian Cystic Fibrosis patients, can cause significant lung disease. Methods We extracted clinical data from a retrospective chart review of 2 CF patients of South Asian descent. Results Patient 1, a 10 year and 11 month old Pakistani female at her initial clinic visit, required multiple hospitalizations for bronchiectasis and pulmonary infections. She was pancreatic sufficient but had slow weight gain. Genetic testing revealed that she is homozygous for the CFTR V456A mutation. Patient 2, an Indian female diagnosed with CF on newborn screening, is compound heterozygous for V456A/R709X. She had slow weight gain with BMI ranging from 12.9 to 13.4 kg/m2 from 3 to 5 years of age and was 14.2 kg/m2 at 6 years of age. At 6 years of age, pulmonary function tests revealed mild lung disease with FVC of 71%, FEV1 of 75%, FEF25–75 of 119%, and FEV1 /FVC of 86% predicted. Sputum cultures were intermittently positive for Staphylococcus aureus and Haemophilus influenza. Conclusions We provide evidence that V456A can cause significant pulmonary disease in South Asian Cystic Fibrosis patients.