title: Fragile x-syndrome: clinical and molecular studies.
abstract: Fragile X-syndrome (FXS) is the most common inherited form of mental disability world-wide. The unique mutation that results in FXS consists of expansion of the CGG trinucleotide repeats (>200) in the 3'untranslated region of the Fragile X mental retardation 1 (FMRI) gene at Xq27.3. The aim of the present study was to evaluate the usefulness of the clinical selection prior to undertaking molecular tests for the diagnosis of patients with FXS. Two hundred males, with unknown cause for their mental retardation were scored on eight Fragile X-features. They were selected from the Human Genetics Clinic, Medical Research Institute, Alexandria University, Egypt. Their ages ranged from 2-20 years. All patients were subjected to clinical genetic examination with special emphasis on Fragile X-features. RNA analysis was performed to detect cases with full FMRI gene mutation. Amplification of FMRI gene by RT-PCR revealed that 34 cases (17%) had full mutation (i.e. more than 200 repeats). Nineteen Fra X cases (56%) were diagnosed after the age of 10 years. A wide range of Fra X-features ranging from 2-7 features were detected in FXS cases. Significant clinical features in FXS diagnosis included family history of MR, large prominent ears, hyperactivity and macro-orchidism (in post pubertal males). One hundred and twenty seven (76.5%) Fra X -ve MR males had one or no Fra X-features. The eight scoring list, used in this study, allows exclusion from further RNA testing in 63.5% of the retarded males. Clinical preselection for RNA testing for FXS in MR males is feasible using a simple scoring list. This will make RNA analysis more cost effective and will facilitate early detection and management of patients with FXS and proper genetic counseling of their families.
authors.affiliation: Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt. akbehery@yahoo.com.
authors.forename: Amal K
authors.initials: AK
authors.lastname: Behery