Research Article

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

Published: December 12, 2017
Genet. Mol. Res. 16(4): gmr16039848 DOI: 10.4238/gmr16039848


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.