Identification of a novel homozygous variant in the MKKS gene in a consanguineous Afghan family with Bardet-Biedl syndrome living in Iran

Retinitis pigmentosa is a collection of heritable retinal dystrophies, in which rod and cone photoreceptor cells of retina die gradually. This disorder can be classified into syndromic and non-syndromic forms. One of the most prevalent syndromic forms of retinitis pigmentosa is Bardet-Biedl syndrome. More than 24 genes have been reported in the pathogenesis of Bardet-Biedl syndrome. One of these genes is MKKS centrosomal shuttling protein. Whole exome sequencing was applied to find the disease-associated variant in an Afghan patient from a consanguineous family living in Iran. This patient and her two brothers have Bardet-Biedl syndrome. Bioinformatics tools were utilized to assess the structural impact of the identified variant. The 3D structure of MKKS protein was predicted, and its model quality was evaluated. The variant was introduced into the wild type model and its structural effects were analyzed. Whole exome sequencing revealed a novel homozygous variant NM_170784.3 (MKKS): c.882A>C; p.(Gln294His), which is segregating with the disease phenotype in the pedigree. Structural modeling showed that this variant does not induce significant global conformational changes in the MKKS protein, but pointed to a possible local effect on the structure around that residue. This finding expands the variant spectrum of MKKS gene in patients with Bardet-Biedl syndrome in an understudied population.