A novel candidate gene, SNRK, causes Bardet-Biedl Syndrome in an Iranian Family

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy disorder with genetic andclinical heterogeneity. Clinical symptoms are widespread and affect various tissues and organs. So far, more than22 different genes have been implicated in Bardet-Biedl syndrome, which almost all of these genes directly orindirectly involved in cilia formation and maintenance. Still, 20% of BBS genetic causes is unknown thatsuggests more unidentified pathogenic loci for this syndrome.Methods: At first, four typical BBS patients were recruited and screened for mutations in a total of 21 knowngenes responsible for inherited retinal diseases, a hallmark symptom of BBS using targeted exome sequencing(TES). TES revealed no pathogenic variant. Then, using next generation sequencing (NGS), all exonic and exonintronboundary variants were filtered in order to identify potentially novel homozygous pathogenic variants.Finally, to determine genetic status, all family members of the proband were screened for detected variants usingSanger sequencing.Results: After close examination, NGS identified a potentially pathogenic candidate variant in SNRK gene[Chr3:43388914C> T; c.C1163T, p.(P388L)] which affects protein function and results in Bardet-Biedl syndromein affected child of a consanguineous Kurdish family. NGS data analysis for the other 3 families are underway.Conclusion: According to strong bioinformatics information and known role of SNRK in metabolism andobesity, this gene is a good candidate for Bardet-Biedl syndrome. However, functional studies in animal modelssuch as zebrafish could be helpful for further confirmation as well as understanding of gene function in ciliaformation and maintenance.

Keywords:

Bardet-Biedl syndrome , SNRK , Whole-exome sequencing , Ciliopathy , Iran