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.

Purpose: To report retinitis pigmentosa and a history of polydactyly in a Bardet-Biedl syndrome mutation carrier. Observations: A 25-year-old male presented to the clinic complaining of poor visual acuity since childhood, night-blindness, and progressive peripheral vision loss. The patient also had a history of polydactyly in both feet. Ophthalmic evaluation was remarkable for a bestcorrected visual acuity of 20/400 in both eyes. Imaging revealed a "salt-and-pepper" appearance surrounding the macula, bone-spicule retinal pigment epithelium hyperplasia, paravenous retinal pigment epithelium hyperplasia, and arteriolar attenuation. In addition, bilateral macular autofluorescence with a surrounding granular hypoautofluorescence and an additional hyperautofluorescent zone was present. Full-field ERG results showed nonrecordable scotopic ERG responses and diminished photopic ERG responses OU, consistent with progressive rod-cone dystrophy. Genetic testing was positive for a pathogenic heterozygous mutation in the BBS1 gene of the variant c.1169T>G (p.Met390Arg) and several variants of uncertain significance in other genes. Conclusions and Importance: Ascertainment of the inheritance patterns in BBS is an evolving discussion. Our case, a BBS carrier with retinitis pigmentosa and a history of polydactyly, could support previous research suggesting non-Mendelian genetics in this ciliopathy. Furthermore, genetic testing and analyses of additional mutations and variants of uncertain significance could potentially explain the reason for BBS-like phenotype in presumed BBS carriers.