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

Mohammad  Dehani; Davood Zare-Abdollahi; Ata   Bushehri; Azadeh   Dehghani; Jalil   Effati; Seyed Ali Mohammad   Miratashi; Hamid Reza  Khorram Khorshid

doi:10.18502/ajmb.v13i4.7214

Mohammad Dehani Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Davood Zare-Abdollahi Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
Ata Bushehri Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Azadeh Dehghani Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran
Jalil Effati Meybod Genetic Research Center, State Welfare Organization, Yazd, Iran
Seyed Ali Mohammad Miratashi Department of Ophthalmology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Hamid Reza Khorram Khorshid Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran

DOI: https://doi.org/10.18502/ajmb.v13i4.7214

Keywords: Bardet–Biedl syndrome, Mutation, Whole exome sequencing

Abstract

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.