Exome Sequencing in 9 Iranian Patients Expands the Mutational and Clinical Spectrum of Bardet–Biedl Syndrome Publisher



Seyedtaghia MR¹ ; Habibi M² ; Hashemigorji F³ ; Tehranifateh S^{4, 5} ; Moghimi P⁶ ; Golestanifar A¹ ; Ghasemi MR^{5, 6} ; Sadeghi H⁷ ; Mirfakhraie R⁷ ; Mousavi P⁸ ; Miryounesi M^{3, 5, 6} ; Salehpour S⁹ Show Affiliations
Source: Biochemical Genetics Published:2025

Abstract

Bardet–Biedl syndrome (BBS, OMIM 209900) is a rare autosomal recessive disorder characterized by a broad spectrum of clinical features including renal anomalies, learning disabilities, postaxial polydactyly, retinal dystrophy, obesity, and hypogonadism. BBS is a heterogeneous syndrome, both genetically and clinically. To date, genetic variants in more than 28 genes have been associated with this syndrome and its subtypes. Most previous studies on BBS have failed to show clear genotype–phenotype correlations. In order to investigate the spectrum of genetic variation among Iranian BBS patients, 9 subjects from 9 different families with clinically diagnosed BBS were included in this study. Following informed consent, we applied exome sequencing (ES) to the proband and their parents. We next performed Sanger sequencing to validate the identified variants. ES successfully detected four known variants: two in the BBS9 gene, c.2014C > T (p.Gln672Ter) and c.1789 + 1 G > A, one variant in the BBS10 gene (c.728_731del; p.Lys243Ilefs*15), and one variant in the MKKS gene (c.515_516del; p.Glu172Alafs*19). ES also detected two new variants in the BBS7 gene, c.880G > C (p.Gly294Arg) and c.719G > A (p.Gly240Asp), one new variant in the CEP290 gene, c.5159C > G (p.Thr1720Arg), and one new variant, in the TTC8 gene, c.462_465del (p.Ser155Glufs*20). In addition, ES identified one novel homozygous deletion of exon 16 in the BBS9 gene. Among the clinical manifestations observed, obesity and polydactyly were the most common findings. Our findings further support the high heterogeneity of BBS: by discovering known, new, and novel pathogenic variants. We expand the mutational spectrum of BBS-related genes and contribute to the understanding of this multisystem disease. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.