Clinical screening and FMR1 gene mutation analysis in male patients with Fragile X syndrome

Abstract

Background: Fragile X syndrome (FXS) is the most prevalent cause of inherited mental retardation in males, with an incidence of 1/4 000 males and 1/8 000 females. 3 molecular alterations have been identified: permutation, full mutation and mosaics, where expanded CGG repeats in the 5´ region surrounding FMR1 gene promoter. Individuals with permutation present between 52 and 200 repeats, whereas full mutations with more than 200 repeats show impaired gene transcription by hypermethylation of FMR1 gene promoter region and absence of FMRP protein, producing mental retardation and specific FXS clinical characteristics.

Objective: The FXS clinical diagnosis is performed using a protocol that considers 15 characteristics; however, the phenotypical differences difficult the exact identification.

Method: 99 male patients referred to INTA with mental retardation and clinical characteristics suggesting FXS were evaluated.

Results: 23 cases present FMR1 full mutation with clinical score 16 to 27 points and 76 cases without mutation with clinical score 10 to 26 points. Comparing both groups, 4 clinical characteristics were significantly different and 3 of them were frequently associated with full mutation, independent of age.

Conclusions: In order to optimize the molecular study of FMR1 gene, the selection of patients should include a clinical screening, so that the study is performed in individuals with clinical score ³ 15 points.