Affiliations: Department Laboratory Medicine, Research Laboratories, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
Note:  Corresponding author: Tester F. Ashavaid, Consultant Biochemist Head, Department of Laboratory Medicine Jt. Director Research, Research Laboratories, P.D. Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai – 400 016, India. Tel.: +91 22 24447935; Fax: +91 22 24442318/24447309; E-mail: [email protected]
Abstract: Cystic fibrosis (CF) has been observed to be far more common in India, than was previously thought. Variability in CF clinical symptoms among individuals, results in diagnostic errors. Also, CF diagnostic facilities are not available at all diagnostic centers across India. Sweat test (gold standard for CF diagnosis) has some limitations. Mutation analysis, therefore, would be useful in detecting the mutant CF alleles in Indian patients. This study, aimed at identifying common CF transmembrane conductance regulator (CFTR) mutations, to develop a molecular diagnostic test in Indian patients, and establish genotype-phenotype correlation. Mutation identification was performed by single stranded conformation polymorphism (SSCP) screening, followed by DNA sequencing of regions with an abnormal SSCP pattern. ∆F508 accounts for about 53% of CF alleles. A substantial proportion of these patients have rare and/or novel mutations. Eight novel and 12 known polymorphisms were also identified. Considering the high percentage of rare/novel mutations, along with ethnic history of Indian population, we can speculate that the remaining uncharacterized mutations might also not be prevalent mutations. The total number of CF disease-causing mutations in Indian patients is very large. Thus, DNA-based population screening will be complicated, and an indirect genetic diagnosis (screening entire gene) would be necessary to characterize all mutations.
Keywords: Cystic fibrosis, sweat chloride, single stranded conformation polymorphism, PCR, India, molecular diagnosis, genotype, phenotype, mutations