Next-Generation Sequencing in the Diagnosis of Patients with Bardet-Biedl Syndrome-New Variants and Relationship with Hyperglycemia and Insulin Resistance.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessively inherited disease with major clinical symptoms such as: obesity, retinal degeneration, polydactyly and renal abnormalities. The aim of the study was to assess the spectrum of gene variants among patients with BBS, identified on the basis of nationwide genetic studies of monogenic diabetes in Polish population. Out of 575 patients enrolled for genetic testing from February 2017 to July 2019, 25 patients with a clinical suspicion of BBS were selected. The identification of pathogenic variants was performed by using targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay (Agilent, Santa Clara, CA, USA). BBS was genetically confirmed in 10 of 25 suspected patients. In patients, 14 different variants were found in six genes, mainly in and gene, including two novel variants. A strong association between hyperglycemia and insulin resistance in patients and the presence of variants in gene was observed. Identification of 14 variants, including two new mutations using the NGS method, is the first molecular characteristic of Polish patients with Bardet-Biedl syndrome. It gives hope for earlier proper diagnosis of BBS in future patients selected from children with early childhood obesity and their medical multidisciplinary care.