Abstract
Bardet-Biedl syndrome (BBS; MIM 209900) is a rare ciliopathy characterized by retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. Mutations in 22 BBS genes have been identified to cause the disease. We report a family with typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, cognitive impairment, and atrioventricular septal defect) mutated in IFT27/BBS19. IFT27 is part of the Intraflagellar transport (IFT), a bidirectional mechanism allowing the protein motility within the cilia. Using whole exome sequencing, two compound heterozygous mutations were found in the proband (NM_006860.4:c.[104A > G];[349+1G > T], p.[Tyr35Cys];[?]) consistent with the expected autosomal recessive inheritance mode. These two mutations have already been reported but independently in other families and lacking either familial segregation or functional validation. This is the third report of IFT27 mutations in BBS patients confirming IFT27 as a BBS gene (BBS19). Mutations in IFT genes (IFT27, IFT172 and IFT74) confirm the IFT-pathway as a pathomechanism for BBS.
Highlights
Bardet-Biedl syndrome (BBS; OMIM 209900) is a recessive and genetically heterogeneous ciliopathy defined by the association of retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, kidney dysfunction and cognitive impairment
We report and validate 2 compound heterozygous mutations in IFT27 confirming the 19th BBS locus in a family with a clear BBS phenotype
Mesoaxial polydactyly of the right hand with a Y-shaped metacarpian and syndactyly between the 5th and the 6th fingers and postaxial polydactyly of the right foot was noticed at birth
Summary
Bardet-Biedl syndrome (BBS; OMIM 209900) is a recessive and genetically heterogeneous ciliopathy defined by the association of retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, kidney dysfunction and cognitive impairment. Mutations in 22 genes have been identified of which WDPCP/BBS15, LZTFL1/BBS17, BBIP1/BBS18 IFT27/BBS19, IFT172/BBS20, C8Orf37/BBS21, and IFT74/BBS22 only account for one or a few families (Khan et al, 2016). Replication of the 19th Bardet-Biedl Syndrome Gene required, respectively, for retrograde and anterograde transport in the cilia. This machinery is part of an essential process for the assembly and the maintenance of the cilia (Taschner and Lorentzen, 2016). Most of the reported mutations in these genes, and in particular for IFT172, have been identified in patients with skeletal forms of ciliopathies including the Jeune asphyxiating thoracic dystrophy (OMIM 208500), Mainzer–Saldino syndrome (OMIM 266920), the Sensenbrenner syndrome (OMIM 218330)
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