Identification of a novel mutation in BBS2 gene in a patient with Bardet-Biedl syndrome

Introduction: Bardet-Biedl syndrome (BBS, OMIM 209900) is an autosomal, recessive, heterogeneous humandisorder characterized by pleiotropic phenotypes including cognitive dysfunction (difficulties with learning andunderstanding), polydactyly, retinal dystrophy, obesity and diabetes, hypogenitalism, kidney anomalies, heartdisease, and hepatic fibrosis. This study evaluates patient with a new pathogenic mutation causing, Bardet-Biedlsyndrome.Material and Methods: The study including a 28-year-old symptomatic male with difficulties with learning andunderstanding retinitis pigmentosa, vision loss, obesity and polydactyly. Blood samples were collected frompatient and relative members of his family. The Genetic Sequencing Test is performed using a custom designedNimblegen chip capturing the genes of interest (19 genes are associated with BBS: BBS1, BBS2, ARL6 (BBS3),BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13),CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), and IFT27(BBS19) followed by Next Generation Sequencing.Result: One mutation c.1228_1229insA (p.Thr410AsnfsX17; Hom) on BBS2 gene has been detected inhomozygous status. Although this mutation has not been reported, its frequencies in normal population are verylow. The frameshift mutation leads to early termination of the amino acid coding, which is expected to affect theprotein’s function. BBS2-related Bardet-Biedl Syndrome 2 is inherited in autosomal recessive manner. Wedetected this mutation in patient’s parents in heterozygous status.Conclusion: The mutation c.1228_1229insA (p.Thr410AsnfsX17) on BBS2 gene has pathogenic effect on BBS2gene expression.

Keywords:

Bardet-Biedl syndrome , Neurodegenerative , Pathogenic mutation