Mutations in GDI1 and X-linked non-specific mental retardation.

ABSTRACT

Mental retardation (MR) is a complex phenotype characterized by suboptimal functioning of the central nervous system (CNS). It is estimated that from 1 to 3% of the general population is affected with MR. MR or "intellectual disability" can be caused by genetic as well as environmental causes that act on the development and functioning of the CNS prenatally, perinatally or postnatally. Genetic causes of MR include chromosome aneusomies, chromosome structural abnormalities, genomic disorders and monogenic diseases. Amongst children, acute MR (QI < 50) is estimated at 0.4% and faint MR is about 2.5-3%. To determine the etiology of the MR, many diagnostic studies have been conducted and they show that MR is very heterogeneous and its etiology is not yet known in 20-50% of the group of patients with severe MR. This percentage increases up to 75-80% in the group of individuals with mild or "borderline" forms of MR. In light of the literature results, we tried to carry out a screening of 41 subjects with nonspecific MR for the detection of mutations in the gene GDI1 using the DHPLC methodology. This technique has the following advantages low cost, high sensitivity (> 95%), and it can be done quickly. We have found 3 nucleotide (nt) substitutions an intronic polymorphism at nt 107877 A --> C, a polymorphism in exon 3 at nt 109259 T --> C (Asn73Asn), and an intronic polymorphism at nt 110314 G --> C. The mutations in this gene are common and do not seem to influence the gene expression so as to cause a change in phenotype. These results therefore do not encourage the research of a diagnostic protocol designed for mutational analysis of the GDI1 human gene as the only responsible factor for a complex disease as Mental Retardation X-linked (MRX).