Molecular Diagnosis of X-Fragile Syndrome: Perspectives for the Public Health System in the Central Region of Brazil

摘要

X-Fragile Syndrome (FXS) is the most common cause of inherited intellectual disability and the second of genetic origin, with an estimated prevalence of 1/4000 men and 1/6000 women. The etiology is associated with a trinucleotide expansion of CGG sequences and hypermethylation of the promoter region of the FMR1 (Fragile-X Mental Retardation-1) gene, located in the Xq27.3 region. Symptoms occur due to lack of Fragile X Mental Retardation Protein (FMRP), essential for dendrites growth and synaptic function. This syndrome is commonly underdiagnosed in children and adolescents due to the high phenotypic variability of patients and the need for a complex and high cost laboratory diagnosis. This research aims to evaluate individuals referred by the public health system of Goiás presenting intellectual deficiency suggestive of FXS and submitted to molecular diagnosis by PCR. Thirty-one patients, ranging in age from 4 to 41 years, were analyzed. It was possible to detect molecular alterations in the FMR1 gene in 6 patients with complete mutations, consistent with the observed phenotypes. The use of molecular techniques associated with capillary electrophoresis in an automatic genetic analyser demonstrated rapid and efficient investigation of CGG repeats in the FMR1 gene. Its inclusion in the public health service, in addition to universalizing access to genetic tests in Brazil, bridging the gap between effective diagnosis and the technologies available until now, has supported families in clarifying the etiology and assessing the risk of recurrence through genetic counselling.