A Genotype-Phenotype Analysis of the Bardet-Biedl Syndrome in Puerto Rico

Background: Bardet-Biedl syndrome is a complex heterogeneous ciliopathy caused by genetic mutations. Although establishing genotype-phenotype correlations has been challenging, some regional variations have been previously reported. Due to its relative geographic isolation, Puerto Rico has a greater prevalence of Bardet-Biedl syndrome than do other regions. We sought to characterize the most frequent genotypic variations in a local cohort of Bardet-Biedl syndrome patients and report any genotypic-phenotypic trends. Methods: Twenty-seven patients from an ophthalmology clinic in Puerto Rico with genetically confirmed Bardet-Biedl syndrome took a questionnaire inquiring about their most common symptoms. Ophthalmological information was obtained from patient records. The frequencies of the genotypic variations and symptoms were calculated. Results: In the study population, BBS1 was the most prevalent mutated gene, followed by BBS7. In the BBS1 group, we found homozygotes for c.1169T>G (p.Met390Arg) and c.1645G>T (p. Glu549*), and compound heterozygotes for c.1169T>G (p.Met390Arg) and c.1645G>T (p. Glu549*), with one patient having c.1645G>T (p.Glu549*) and c.432+1G>A (splice donor). All the BBS7 patients were homozygous for c.632C>T (p.Thr211Ile). Compared to BBS7, we found that BBS1 patients generally had a milder ocular and systemic phenotype. However, when analyzing different BBS1 variants, patients with mutations in c.1645G>T (p.Glu549*), both compound heterozygous and homozygous, had more severe systemic phenotypes, overall. Conclusion: Our study was the first detailed genotype-phenotype analysis of the Bardet- Biedl syndrome in Puerto Rico. Genetic mutations in BBS1 and BBS7 seem to be the most common culprits behind Bardet-Biedl syndrome in this population. Although patients diagnosed with BBS1 are likely to display milder systemic features, this was not the case with our BBS1 patients having the c.1645G>T (p.Glu549*) mutation. Further studies should focus on the c.1645G>T (p.Glu549*) mutation's impact on the BBS1 gene and protein product.

Automated summary

This study provides the first detailed genotype-phenotype analysis of Bardet-Biedl syndrome in Puerto Rico, revealing that mutations in BBS1 and BBS7 are the most common culprits in this population. While patients with BBS1 mutations generally exhibit milder symptoms, those with the c.1645G>T (p.Glu549*) mutation tend to have more severe phenotypes. Further research should focus on understanding the impact of the c.1645G>T (p.Glu549*) mutation on the BBS1 gene and protein product.