Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: experience from India

Very little is known about the genetics of cystic fibrosis (CF) from the Indian subcontinent. The aims of the study were to identify the mutations and study the relation of genotype with phenotype in Indian children with CF.

A total of 100 patients with CF were screened for mutations in the CFTR gene. These included c.1521_1523delCTT (p.F508del) and c.3849+10 kb C>T mutations followed by single strand conformation polymorphism/heteroduplex analysis for mutations in 19 out of 27 exons of the CFTR gene.

At least one mutation was identified in 40 patients. The most common mutation identified was p.F508del; 20 patients were homozygous and 13 heterozygous. In addition, c.3849+10 kb C>T, c.1161delC, and p.S549N were identified in two patients each and p.R352Q, p.R1158X and p.R75Q were identified in one patient each. Three novel mutations, viz. c.1002-7_1002-5delTTT, p.G149X and p.L183I were also identified. Majority of patients who were p.F508del positive originated from Pakistan and north-western states of India. The phenotypes of all patients were classical. Genotype-phenotype correlation revealed that p.F508del positive patients had a more severe disease, manifesting at an earlier age.

A strategy for mutation screening for CF in India must involve testing for p.F508del followed by c.1161delC, c.3849+10 kb C>T and p.S549N. There is a need for large multicentric studies using more sensitive techniques for the identification of mutations in Indian CF patients.