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. 2019 Jun 13;45(1):72.
doi: 10.1186/s13052-019-0659-1.

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

Elena Manara  1 , Stefano Paolacci  2 , Fabiana D'Esposito  2   3   4 , Andi Abeshi  2 , Lucia Ziccardi  5 , Benedetto Falsini  6   7 , Leonardo Colombo  8 , Giancarlo Iarossi  9 , Alba Pilotta  10 , Loredana Boccone  11 , Giulia Guerri  2 , Marica Monica  11 , Balzarini Marta  11 , Paolo Enrico Maltese  12 , Luca Buzzonetti  9 , Luca Rossetti  8 , Matteo Bertelli  2
Affiliations

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

Elena Manara et al. Ital J Pediatr. .

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.

Keywords: Bardet-Biedl syndrome; Genetic diagnosis; triallelic inheritance; NGS.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of the cilium and intraflagellar transport. 1. transition zone; 2. basal body; 3. axoneme; 4. pericentriolar area. BBS-chaperonin complex (BBS6, BBS10, BBS12) binds and stabilizes the BBS protein to form the BBSome (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9, BBS17, BBS18). BBSome plays a critical role in the regulation of cilia composition and in intraflagellar trafficking. Indeed, transmembrane (TM) and periferal membrane protein are transported in the cilium in a BBSome dependent manner. BBS3 triggers BBSome complex /cargo proteins interaction and their transition across the control barrier (transition zone - BBS13, BBS14, BBS15) into the cilium. In bold, genes included in our NGS panel
See this image and copyright information in PMC

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