Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa

Pathogenic variants (mutations) in the Abelson helper integration site 1 (AHI1) gene are known to be associated with Joubert syndrome, a developmental disorder causing visual, cognitive and motor deficits. In this study, we show that some pathogenic variants in the AHI1 gene can cause visual impairment, without other symptoms or signs suggestive of Joubert syndrome. Such variants were located in a specific domain (WD40 domain) of the encoded protein and have only subtle effects when expressed in cells in culture. The data support the hypothesis that these “non-syndromic” variants give residual protein function, while alleles associated with Joubert syndrome completely abolish function. (By Dr. Lonneke Haer-Wigman, http://jmg.bmj.com/content/early/2017/06/24/jmedgenet-2016-104200 )