P127 – 2762: Micro duplication in OPHN1: Novel possibilty of X-LID cerebellar hypoplasia syndrome (OPHN1 syndrome)

Abstract

Oligophrenin-1 (OPHN1) encodes a Rho GTPase-activating protein (RhoGAP) whose loss of function is associated with a rare X-linked intellectual disability (X-LID), with specific features and cerebellar hypoplasia involving the vermis. Mutations in OPHN1, located in Xq12, is the most likely to be found, but deletions were also described. We report 2 male siblings with intellectual disability issued from a family with history of X-LID. Morphology recalled the one in OPHN1 syndrome affected patients, with deep-set eyes, marked infra orbital creases, long face and prominent chin. Brain MRI showed slight vermis hypoplasia and moderate asymmetric ventricular dilatation. Sequencing of OPHN1 was performed but no mutation was found. Array comparative genomic hybridization revealed a micro duplication of 172 Kb, mapped on Xq12, inherited from the mother. The proximal breakpoint due to this micro duplication disrupts OPHN1 and probably disturbs the function of RhoGAP. Functional analysis is ongoing.