Genotype-Phenotype Correlation in Children With Cystic Fibrosis From India: A Multicentric Study.

Area of Science:

• Medical Genetics
• Pediatric Pulmonology
• Genetic Diseases

Background:

• Cystic Fibrosis (CF) is a genetic disorder with variable clinical presentations.
• Genotype-phenotype correlations are crucial for understanding CF heterogeneity.
• Next-generation sequencing (NGS) enables comprehensive genetic analysis in CF patients.

Purpose of the Study:

• To investigate genotype-phenotype correlations in a cohort of children with cystic fibrosis.
• To identify specific CFTR variants and their association with clinical manifestations.
• To compare phenotypic features between different genetic groups.

Main Methods:

• Prospective, multicenter study involving 260 children with cystic fibrosis.
• Initial testing for two common CFTR variants, followed by exome sequencing using NGS.
• Analysis of genotype data against clinical phenotypes including age at diagnosis, pancreatic insufficiency, and sweat chloride values.

Main Results:

• Boys and consanguinity were more prevalent in patients with non-c.1520_1522del variants.
• The 3849+10kbC>T variant was associated with less pancreatic insufficiency, later diagnosis, and lower sweat chloride.
• Homozygous variants correlated with younger age at diagnosis and higher pancreatic insufficiency compared to compound heterozygotes.

Conclusions:

• Genotype-phenotype correlations in pediatric cystic fibrosis are significant.
• The 3849+10kbC>T variant presents unique clinical characteristics.
• Genetic variants influence key CF outcomes like age at diagnosis and pancreatic function.