Novel mutation in MKKS/BBS6 linked with arRP and polydactyly in a family of North Indian origin

Background To identify the underlying genetic defect in a fourth‐generation autosomal recessive retinitis pigmentosa (arRP) family. Detailed family history and clinical data were collected from nine members, including three affected, from an arRP family. Methods Whole‐exome sequencing (WES) was performed on DNA sample of an affected individual IV: 2. Variants obtained by WES were annotated using Ion Reporter Software (ver. 5.2). Potential pathogenic variants detected in an affected member were validated in other affected and unaffected family members by Sanger sequencing. Further 150 ethnically‐matched controls were tested for the variant that co‐segregated completely with disease in the family, so as to exclude it as a polymorphism. Various web‐based bioinformatics tools were also applied to access pathogenic potential of the observed variant. Results All the three patients had RP with polydactyly of both hands and feet, however, they did not show other symptoms of Bardet‐Biedl syndrome (BBS) or McKusick‐Kaufmann Syndrome (MKKS). A novel missense mutation, that is, c.518A>C (p.His173Pro) was identified in MKKS/BBS6 that co‐segregated completely with the disease phenotype in all the three affected members and was not observed in six unaffected members of the family. Also the c.518A>C change was not observed in 150 ethnically matched controls (300 chromosomes), hence excluding it as a polymorphism. Conclusions Present study is the second report of identifying a novel mutation in MKKS/BBS6 that is linked with arRP in association with polydactyly, however, with no other signs of BBS or MKKS. These findings further expand the mutation spectrum of MKKS/BBS6 for arRP with polydactyly.