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© 2021. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
A Genotype–Phenotype Analysis of the Bardet–Biedl Syndrome in Puerto Rico
Author
Guardiola, Gabriel A; Ramos, Fabiola; Izquierdo, Natalio J; Oliver, Armando L
Pages
3757-3764
Section
Original Research
Publication year
2021
Publication date
2021
Publisher
Taylor & Francis Ltd.
ISSN
1177-5467
e-ISSN
1177-5483
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2573623004
Copyright
© 2021. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.