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Ital J Pediatr. 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.

Author information

1
Magi Euregio, Bolzano, Italy. elena.manara@assomagi.org.
2
Magi Euregio, Bolzano, Italy.
3
Imperial College Ophthalmic Research Unit, Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK.
4
Eye Clinic, Department of Neurosciences, Reproductive Sciences and Dentistry, Federico II University, Naples, Italy.
5
IRCCS - Fondazione Bietti, Rome, Italy.
6
Institute of Ophthalmology, Università Cattolica del Sacro Cuore, Rome, Italy.
7
Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy.
8
Department of Ophthalmology, San Paolo Hospital, University of Milan, Milan, Italy.
9
Department of Ophthalmology, Bambino Gesù IRCCS Children's Hospital, Rome, Italy.
10
Special Unit of Auxoendocrinology, Diabetology and Pediatric Genetics, University of Brescia, Spedali Civili di Brescia, Brescia, Italy.
11
Microcitemic Regional Hospital, Brotzu Hospital, Cagliari, Italy.
12
MAGI'S Lab, Rovereto, Italy.

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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