Identification of a Novel Homozygous Mutation in BBS10 Gene in an Iranian Family with Bardet-Biedl Syndrome

en 34900151 Identification of a Novel Homozygous Mutation in BBS10 Gene in an Iranian Family with Bardet-Biedl Syndrome Background: Bardet–Biedl Syndrome (BBS) is a rare pleiotropic autosomal recessive disease related to ciliopathies with approximately 25 causative genes. BBS is a multisystemic disorder with wide spectrum of manifestations including truncal obesity, retinal dystrophy, male hypogenitalism, postaxial polydactyly, learning difﬁculties, and renal abnormalities. Methods: A consanguineous Iranian family with a 28-year-old daughter affected with BBS, resulting from a first cousin marriage, was examined. After clinical examination, Whole Exome Sequencing (WES) was applied. Following the analysis of exome data, Sanger sequencing was used to confirm as well as to co-segregate the candidate variant with the phenotype. Results: A novel homozygous variant [c. 2035G>A (p.E679K)] in exon 2 of the BBS10 gene was found which was categorized as likely pathogenic based on American College of Medical Genetics and Genomics (ACMG) guidelines and criteria. In this study, the variant was fully co-segregated with the phenotype in the family. Conclusion: Despite overlapping with other ciliopathies in terms of the phenotype, the BBS has high genetic heterogeneity and clinical variability even among affected members of a family. The symptoms observed in patients are largely related to the genes involved and the type of mutations in the BBS. In this study, in addition to phenotype description of the proband harboring a novel disease-causing variant in BBS10 gene, the spectrum of BBS symptoms was expanded. The findings of this study can be useful in genetic counseling, especially for risk estimation and prenatal diagnosis. Bardet–Biedl syndrome, Mutation, Whole exome sequencing 230 233 https://www.ajmb.org/En/Article.aspx?id=40482 https://www.ajmb.org/PDF/En/FullText/40482.pdf MohammadDehaniGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran71792DavoodZare-Abdollahi11425AtaBushehri Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran71793AzadehDehghani Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran71794JalilEffatiMeybod Genetic Research Center, State Welfare Organization, Yazd, Iran71795Seyed Ali MohammadMiratashi Department of Ophthalmology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran71796Hamid RezaKhorram KhorshidFetal Health Research Center, Hope Generation Foundation, Tehran, Iran42