Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitor

Non-specific X-linked mental retardation (MRX) is a very common disorder which affects ∼1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly be-cause of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collabora-tive study using the candidate gene approach demon-strated the presence of mutations in GDIα, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIα is mainly a brain-specific protein that plays a criti-cal role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of muta-tions in the GDIα in mentally retarded patients and t