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Functional modelling of a novel mutation in BBS5

Lookup NU author(s): Mohamed Al-Hamed, Dr Charles van Lennep, Dr Ann Marie Hynes, Paul Chrystal, Dr Lorraine Eley, Dr Reham El Sayed, Dr Roslyn Simms, Professor John SayerORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy disorder with 18 known causative genes (BBS1-18). The primary clinical features are renal abnormalities, rod-cone dystrophy, post-axial polydactyly, learning difficulties, obesity and male hypogonadism.Results: We describe the clinical phenotype in three Saudi siblings in whom we have identified a novel mutation in exon 12 of BBS5 (c.966dupT; p.Ala323CysfsX57). This single nucleotide duplication creates a frame shift results in a predicted elongated peptide. Translation blocking Morpholino oligonucleotides were used to create zebrafish bbs5 morphants. Morphants displayed retinal layering defects, abnormal cardiac looping and dilated, cystic pronephric ducts with reduced cilia expression. Morphants also displayed significantly reduced dextran clearance via the pronephros compared to wildtype embryos, suggesting reduced renal function in morphants. The eye, kidney and heart defects reported in morphant zebrafish resemble the human phenotype of BBS5 mutations. The pathogenicity of the novel BBS5 mutation was determined. Mutant mRNA was unable to rescue pleiotropic phenotypes of bbs5 morphant zebrafish and in cell culture we demonstrate a mislocalisation of mutant BBS5 protein which fails to localise discretely with the basal body.Conclusions: We conclude that this novel BBS5 mutation has a deleterious function that accounts for the multisystem ciliopathy phenotype seen in affected human patients. © 2014 Al-Hamed et al.; licensee BioMed Central Ltd.

Publication metadata

Author(s): Al-Hamed MH, van Lennep C, Hynes AM, Chrystal P, Eley L, Al-Fadhly F, El Sayed R, Simms RJ, Meyer B, Sayer JA

Publication type: Article

Publication status: Published

Journal: Cilia

Year: 2014

Volume: 3

Online publication date: 21/02/2014

Acceptance date: 04/02/2014

Date deposited: 18/10/2018

ISSN (electronic): 2046-2530

Publisher: BioMed Central Ltd


DOI: 10.1186/2046-2530-3-3


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