Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study
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 definitio...
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-06-01
|
Series: | Italian Journal of Pediatrics |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13052-019-0659-1 |
id |
doaj-baad0fff401c40fabb59d9e3e75bf2e8 |
---|---|
record_format |
Article |
spelling |
doaj-baad0fff401c40fabb59d9e3e75bf2e82020-11-25T03:26:03ZengBMCItalian Journal of Pediatrics1824-72882019-06-014511810.1186/s13052-019-0659-1Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian studyElena Manara0Stefano Paolacci1Fabiana D’Esposito2Andi Abeshi3Lucia Ziccardi4Benedetto Falsini5Leonardo Colombo6Giancarlo Iarossi7Alba Pilotta8Loredana Boccone9Giulia Guerri10Marica Monica11Balzarini Marta12Paolo Enrico Maltese13Luca Buzzonetti14Luca Rossetti15Matteo Bertelli16Magi EuregioMagi EuregioMagi EuregioMagi EuregioIRCCS – Fondazione BiettiInstitute of Ophthalmology, Università Cattolica del Sacro CuoreDepartment of Ophthalmology, San Paolo Hospital, University of MilanDepartment of Ophthalmology, Bambino Gesù IRCCS Children’s HospitalSpecial Unit of Auxoendocrinology, Diabetology and Pediatric Genetics, University of Brescia, Spedali Civili di BresciaMicrocitemic Regional Hospital, Brotzu HospitalMagi EuregioMicrocitemic Regional Hospital, Brotzu HospitalMicrocitemic Regional Hospital, Brotzu HospitalMAGI’S LabDepartment of Ophthalmology, Bambino Gesù IRCCS Children’s HospitalDepartment of Ophthalmology, San Paolo Hospital, University of MilanMagi EuregioAbstract 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.http://link.springer.com/article/10.1186/s13052-019-0659-1NGSBardet-Biedl syndromeGenetic diagnosis; triallelic inheritance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study Italian Journal of Pediatrics NGS Bardet-Biedl syndrome Genetic diagnosis; triallelic inheritance |
author_facet |
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 |
author_sort |
Elena Manara |
title |
Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study |
title_short |
Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study |
title_full |
Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study |
title_fullStr |
Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study |
title_full_unstemmed |
Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study |
title_sort |
mutation profile of bbs genes in patients with bardet–biedl syndrome: an italian study |
publisher |
BMC |
series |
Italian Journal of Pediatrics |
issn |
1824-7288 |
publishDate |
2019-06-01 |
description |
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. |
topic |
NGS Bardet-Biedl syndrome Genetic diagnosis; triallelic inheritance |
url |
http://link.springer.com/article/10.1186/s13052-019-0659-1 |
work_keys_str_mv |
AT elenamanara mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT stefanopaolacci mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT fabianadesposito mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT andiabeshi mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT luciaziccardi mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT benedettofalsini mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT leonardocolombo mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT giancarloiarossi mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT albapilotta mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT loredanaboccone mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT giuliaguerri mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT maricamonica mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT balzarinimarta mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT paoloenricomaltese mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT lucabuzzonetti mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT lucarossetti mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy AT matteobertelli mutationprofileofbbsgenesinpatientswithbardetbiedlsyndromeanitalianstudy |
_version_ |
1724594158519189504 |