Molecular Basis of Cystic Fibrosis Disease: An Indian Perspective

Abstract

Cystic fibrosis is a common autosomal recessive disorder usually found in population of white Caucasian descent. Now it is well documented the presence of CF disease in India with the advancement of laboratory testing. As once it was thought non existence of this disease in our population. Most of the phenotype of CF disease was in accordance of western population. Genetic analysis of CFTR gene in Indian CF patients revealed that most common mutation was delta F508 mutation. However, it was less than Caucasian population. CFTR mutations are also a causative factor in the pathogenesis of male infertility due to obstructive azoospermia. There are two most common mutation viz. IVS8-T5 and delta F508 which are responsible for congenital absence of vas deferens in male infertility patients. Elevated levels of sweat chloride at two occasions along with the presence of two mutations in CFTR gene was gold standard method for diagnosis of CF disease. It is noteworthy here that due to magnitude of Indian population, the total CF disease load would be more than many European countries. Clinical data demonstrate the prevalence of both classical and genetic form of CF in India.

Evaluation of micronutrient profile of North Indian children with cystic fibrosis: a case–control study

“…c ystic fibrosis (CF) is an autosomal recessive disorder with multiple organ involvement (1). CF is being increasingly recognized in the Indian subcontinent due to increased awareness among pediatricians, although its precise magnitude is not known.…”

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

“…Others have drawn attention to the low clinical utility of current targeted mutation panels outside of European populations, but, to our knowledge, this report is the first systematic, quantitative demonstration of population bias with a large, genetically diverse data set. 5,[27][28][29] Our classification system and method of discovery have general utility for other recessive disease genes. The presence of an analytical bias in identifying CFTR mutations on carrier screening panels calls into question whether this bias is present among all disease-associated genes tested by current platforms, especially those not as well annotated as CFTR.…”

“…Based on the static European definition of classic CF, the disease was thought to be exceedingly rare in South and East Asia. 27,29 Many mutations that cause classic CF were identified in Europeans after the discovery of the CFTR gene in 1989 and the ensuing analysis of patient DNA sequences. At the same time, additional protein-changing CFTR variants were discovered in association with diseases that had been thought to have etiologies distinct from CF.…”

“…1 Different populations have particular CFTR allele spectra that are associated with distinct manifestations of disease. 4,27,29 A system for scoring CFTR disease liability needs to focus on the degree to which a defined mutation increases morbidity and mortality in certain ancestral backgrounds, irrespective of a narrow presentation of disease symptoms. Ours is not the first application of computational analysis to novel variants in the CFTR gene.…”

The Main Pathogenetic Constituents of Comorbid Chronic Obstructive Pulmonary Disease and Chronic Pancreatitis (Literature Review)

“…Cystic fibrosis is a hereditary disease with autosomalrecessive type of inheriting characterized by CF gene mutation resulting in changes of the protein structure of CF transmembrane conductivity regulator (CFTCR) functioning as цАМФ-dependent ion channels responsible for the transport of chlorine and sodium ions, and located on the apical surface of the epithelial cells (lungs, liver, intestine, pancreas, sweat glands, reproductive organs) [17,39,42]. Ion channels regulating transport of sodium and chlorine ions provide appropriate hydration and ion content of bronchial secretion [44].…”