Abstract

Joubert syndrome (JS) disease is a clinically and genetically heterogeneous disorder with mutations in more than 35 genes involved in its pathogenicity. Molecular genetic methods including next generation sequencing (NGS) and Sanger sequencing are effective techniques used for identifying rare genetic variants that have a strong effect on disease pathogenesis. In this study, we tested a large pedigree with a history of several affected members with JS. At first the proband was sequenced by NGS technique then, confirmed by sanger sequencing method. After this, all available members of the pedigree were subjected to molecular analysis by sanger sequencing technique. The results of this study showed a novel variant in the C5ORF42 gene c.3080A > T: p. D1027V leading to a substitution of a valine for aspartic acid (D1027V) and may be associated with JS. This variant was present in proband compatible with autosomal recessive pattern. Also this variant was present in all parents (both father and mother) of affected individuals in a heterozygous state. It seems that mutations in C5ORF42 gene are associated with JS. However, the substantial mechanism requires further investigation.