Akademik Veri Yönetim Sistemi
15. Ulusal Tıbbi Genetik Kongresi, Muğla, Türkiye, 9 - 13 Kasım 2022, ss.153
Introduction: Bardet-Biedl Syndrome (BBS) is an ultra-rare disorder characterized by obesity, retinal dystrophy, polydactyly, renal malformation, mental retardation, and hypogonadism. The syndrome's prevalence is estimated to be 1 in 100,000 live births. BBS is a genetically heterogeneous syndrome which is associated with more than 20 different genes. BBS genes encode BBS proteins which are localized to the centrosome and regulate the biogenesis and functions of the cilia. Purpose: This study aims to determine the effectiveness of the multigene panel testing in patients who have BBS clinical features and to reveal the genetic etiology of the BBS patients. Method: Twenty probands having specific examination findings related to Bardet Biedl syndrome were included in this study. After evaluation of clinical and family histories, probands were screened using a custom-designed Bardet Biedl syndrome panel including 22 genes via next-generation sequencing (NGS). The family members of the probands carrying pathogenic variations were screened via Sanger Sequencing. Results: Among 20 cases major clinical finding were polydactyly (n=15)(75%), obesity (n=13)(65%), and retinal dystrophy (n=8)(40%). The ages of the probands ranged from two months to 45 years. We detected in 10 (50%) probands biallelic pathogenic variations, which of 2 were novel, in BBS10(n=3), BBS9(n=2), MKKS(n=2), BBS1(n=1), BBS7(n=1), BBS4(n=1) genes. Also, we detected in 3(15%) probands biallelic variations, these variants were reported as Variant of uncertain significance (VUS) at the Clinvar Database in BBS1(n=2), and BBS4(n=1) genes. BBS diagnosis was present in the families of three cases in which the pathogenic variants were segregated with the disease. Conclusion: The detection of two novel pathogenic variations has contributed to the expansion of the mutation spectrum. Also, the confirmation of clinical diagnosis in 50% of the patients with molecular genetic testing supports that the screening related genes via NGS panel is an effective diagnostic method for BBS. Defining the molecular etiology of BBS is important in terms of screening at-risk family members and providing appropriate genetic counseling for preimplantation genetic diagnosis opportunities.