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Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and impro...

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Autores principales: Esposito, Gabriella, Testa, Francesco, Zacchia, Miriam, Crispo, Anna Alessia, Di Iorio, Valentina, Capolongo, Giovanna, Rinaldi, Luca, D’Antonio, Marcella, Fioretti, Tiziana, Iadicicco, Pasquale, Rossi, Settimio, Franzè, Annamaria, Marciano, Elio, Capasso, Giovanbattista, Simonelli, Francesca, Salvatore, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286791/
https://www.ncbi.nlm.nih.gov/pubmed/28143435
http://dx.doi.org/10.1186/s12881-017-0372-0
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author Esposito, Gabriella
Testa, Francesco
Zacchia, Miriam
Crispo, Anna Alessia
Di Iorio, Valentina
Capolongo, Giovanna
Rinaldi, Luca
D’Antonio, Marcella
Fioretti, Tiziana
Iadicicco, Pasquale
Rossi, Settimio
Franzè, Annamaria
Marciano, Elio
Capasso, Giovanbattista
Simonelli, Francesca
Salvatore, Francesco
author_facet Esposito, Gabriella
Testa, Francesco
Zacchia, Miriam
Crispo, Anna Alessia
Di Iorio, Valentina
Capolongo, Giovanna
Rinaldi, Luca
D’Antonio, Marcella
Fioretti, Tiziana
Iadicicco, Pasquale
Rossi, Settimio
Franzè, Annamaria
Marciano, Elio
Capasso, Giovanbattista
Simonelli, Francesca
Salvatore, Francesco
author_sort Esposito, Gabriella
collection PubMed
description BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and improve its diagnosis and treatment, we evaluated the genotype-phenotype relationship in patients with a molecular diagnosis of BBS. METHODS: We analyzed three common BBS genes, BBS1, BBS10 and BBS2, in 25 Italian patients fulfilling the clinical criteria of BBS. In 12 patients, we identified gene-specific biallelic variants and thus correlated genotype to the ophthalmic, renal and audio-vestibular phenotypes. RESULTS: At least one sequence variant was found in 60% of patients. The most common mutated gene was BBS1 followed by BBS10. Of the 17 sequence variants we found, 11 have not previously been associated with BBS. In 12 patients, we identified biallelic pathogenic variants; they had retinitis pigmentosa with early onset of visual impairment. However, retinal dystrophy was less severe in patients with BBS1 than in those with BBS10 variants. Overall, we found a high prevalence of renal dysmorphism and dysfunction. Notably, patients with BBS10 variants had the most severe renal impairment, which resulted in a critical decline in renal function. All the patients who underwent audio-vestibular evaluation had dysfunction of the cochlear outer hair cells, thus confirming the presence of hearing defects. CONCLUSION: BBS1, BBS2 and BBS10 are major causative genes in Italian BBS patients. BBS10 was associated with the worse outcome in terms of the renal, ocular and audiovestibular phenotypes. Cochlear dysfunction should be included among the hallmarks of BBS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-017-0372-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-52867912017-02-06 Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants Esposito, Gabriella Testa, Francesco Zacchia, Miriam Crispo, Anna Alessia Di Iorio, Valentina Capolongo, Giovanna Rinaldi, Luca D’Antonio, Marcella Fioretti, Tiziana Iadicicco, Pasquale Rossi, Settimio Franzè, Annamaria Marciano, Elio Capasso, Giovanbattista Simonelli, Francesca Salvatore, Francesco BMC Med Genet Research Article BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and improve its diagnosis and treatment, we evaluated the genotype-phenotype relationship in patients with a molecular diagnosis of BBS. METHODS: We analyzed three common BBS genes, BBS1, BBS10 and BBS2, in 25 Italian patients fulfilling the clinical criteria of BBS. In 12 patients, we identified gene-specific biallelic variants and thus correlated genotype to the ophthalmic, renal and audio-vestibular phenotypes. RESULTS: At least one sequence variant was found in 60% of patients. The most common mutated gene was BBS1 followed by BBS10. Of the 17 sequence variants we found, 11 have not previously been associated with BBS. In 12 patients, we identified biallelic pathogenic variants; they had retinitis pigmentosa with early onset of visual impairment. However, retinal dystrophy was less severe in patients with BBS1 than in those with BBS10 variants. Overall, we found a high prevalence of renal dysmorphism and dysfunction. Notably, patients with BBS10 variants had the most severe renal impairment, which resulted in a critical decline in renal function. All the patients who underwent audio-vestibular evaluation had dysfunction of the cochlear outer hair cells, thus confirming the presence of hearing defects. CONCLUSION: BBS1, BBS2 and BBS10 are major causative genes in Italian BBS patients. BBS10 was associated with the worse outcome in terms of the renal, ocular and audiovestibular phenotypes. Cochlear dysfunction should be included among the hallmarks of BBS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-017-0372-0) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-01 /pmc/articles/PMC5286791/ /pubmed/28143435 http://dx.doi.org/10.1186/s12881-017-0372-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Esposito, Gabriella
Testa, Francesco
Zacchia, Miriam
Crispo, Anna Alessia
Di Iorio, Valentina
Capolongo, Giovanna
Rinaldi, Luca
D’Antonio, Marcella
Fioretti, Tiziana
Iadicicco, Pasquale
Rossi, Settimio
Franzè, Annamaria
Marciano, Elio
Capasso, Giovanbattista
Simonelli, Francesca
Salvatore, Francesco
Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title_full Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title_fullStr Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title_full_unstemmed Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title_short Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
title_sort genetic characterization of italian patients with bardet-biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286791/
https://www.ncbi.nlm.nih.gov/pubmed/28143435
http://dx.doi.org/10.1186/s12881-017-0372-0
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