Mutation profile of BBS genes in patients with Bardet-Biedl syndrome: an Italian study

Elena Manara, Stefano Paolacci, Fabiana D'Esposito, Andi Abeshi, Lucia Ziccardi, Benedetto Falsini, Leonardo Colombo, Giancarlo Iarossi, Alba Pilotta, Loredana Boccone, Giulia Guerri, Marica Monica, Balzarini Marta, Paolo Enrico Maltese, Luca Buzzonetti, Luca Rossetti, Matteo Bertelli

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy.

METHODS: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients.

RESULTS: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes.

CONCLUSIONS: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified.

Original languageEnglish
Pages (from-to)72
JournalItalian Journal of Pediatrics
Volume45
Issue number1
DOIs
Publication statusPublished - Jun 13 2019

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Bardet-Biedl Syndrome
Mutation
Genes
Multifactorial Inheritance
Chaperonins
Phenotype
Hypogonadism
Genetic Association Studies
Therapeutics
Genotype
Morbidity
Kidney

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Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : an Italian study. / Manara, Elena; Paolacci, Stefano; D'Esposito, Fabiana; Abeshi, Andi; Ziccardi, Lucia; Falsini, Benedetto; Colombo, Leonardo; Iarossi, Giancarlo; Pilotta, Alba; Boccone, Loredana; Guerri, Giulia; Monica, Marica; Marta, Balzarini; Maltese, Paolo Enrico; Buzzonetti, Luca; Rossetti, Luca; Bertelli, Matteo.

In: Italian Journal of Pediatrics, Vol. 45, No. 1, 13.06.2019, p. 72.

Research output: Contribution to journalArticle

Manara, E, Paolacci, S, D'Esposito, F, Abeshi, A, Ziccardi, L, Falsini, B, Colombo, L, Iarossi, G, Pilotta, A, Boccone, L, Guerri, G, Monica, M, Marta, B, Maltese, PE, Buzzonetti, L, Rossetti, L & Bertelli, M 2019, 'Mutation profile of BBS genes in patients with Bardet-Biedl syndrome: an Italian study', Italian Journal of Pediatrics, vol. 45, no. 1, pp. 72. https://doi.org/10.1186/s13052-019-0659-1
Manara, Elena ; Paolacci, Stefano ; D'Esposito, Fabiana ; Abeshi, Andi ; Ziccardi, Lucia ; Falsini, Benedetto ; Colombo, Leonardo ; Iarossi, Giancarlo ; Pilotta, Alba ; Boccone, Loredana ; Guerri, Giulia ; Monica, Marica ; Marta, Balzarini ; Maltese, Paolo Enrico ; Buzzonetti, Luca ; Rossetti, Luca ; Bertelli, Matteo. / Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : an Italian study. In: Italian Journal of Pediatrics. 2019 ; Vol. 45, No. 1. pp. 72.
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T1 - Mutation profile of BBS genes in patients with Bardet-Biedl syndrome

T2 - an Italian study

AU - Manara, Elena

AU - Paolacci, Stefano

AU - D'Esposito, Fabiana

AU - Abeshi, Andi

AU - Ziccardi, Lucia

AU - Falsini, Benedetto

AU - Colombo, Leonardo

AU - Iarossi, Giancarlo

AU - Pilotta, Alba

AU - Boccone, Loredana

AU - Guerri, Giulia

AU - Monica, Marica

AU - Marta, Balzarini

AU - Maltese, Paolo Enrico

AU - Buzzonetti, Luca

AU - Rossetti, Luca

AU - Bertelli, Matteo

PY - 2019/6/13

Y1 - 2019/6/13

N2 - BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy.METHODS: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients.RESULTS: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes.CONCLUSIONS: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified.

AB - BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy.METHODS: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients.RESULTS: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes.CONCLUSIONS: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified.

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