Síndrome de Bardet-Biedl en la India: Espectro Genotípico y Características Clínicas de una Cohorte de un Solo Centro

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy with multisystem involvement. While BBS1 mutations are common globally, population-specific genetic patterns and phenotype severity vary. This study aimed to investigate genotype-phenotype correlations in an Indian cohort.

In this single-centre, observational cohort study, individuals meeting Beales' clinical criteria for BBS underwent next-generation sequencing (NGS). Phenotypic features were correlated with underlying genotypes, with particular attention to the type of mutation (truncating vs. non-truncating) and the implicated gene subgroup (chaperonin-like vs. BBSome complex).

Of 15 patients screened, nine were confirmed to have BBS. The most frequently mutated genes were BBS10 and BBS2 (33.3% each), followed by BBS9 and BBS12. All variants were homozygous, with truncating mutations observed in 77.8% of cases. Obesity was universally present, while retinal dystrophy and polydactyly were each seen in 88.9% of patients. Renal abnormalities were less frequent (22.2%) and were observed only among patients with truncating variants in this cohort. Compared with non-truncating mutations, truncating variants were associated with earlier diagnosis (median age: 14 vs. 28.5 years), possibly reflecting earlier clinical manifestations. Notably, earlier onset of disease and broader multisystem involvement were more frequently observed in patients with BBS10 mutations.

This study provides descriptive insights into the genotypic spectrum of BBS in an Indian cohort, with frequent involvement of BBS10 and BBS2. The findings underscore the importance of population-specific genetic data and highlight the potential value of early genetic evaluation in consanguineous families.