Short Communication Screening for fragile X syndrome in males from specialized institutions in the northeast region of Brazil

Abstract

ABSTRACT. The objective of this study was to perform a study of fragile X syndrome (FXS) in São Luís, Maranhão, in males residing in five specialized institutions. Two hundred thirty-eight males with intellectual disability of unknown etiology participated in this study. Blood samples were processed and stored until DNA extraction. Screening for FMR1 gene mutations was performed using non-isotopic polymerase chain reaction amplification and DNA sequencing using an ABI Prism 3130 automated sequencer. Two individuals (0.84%) were positive for FMR1 mutations. One had a mutation due to expansion of the CGG M.T.M. Viveiros et al. 6898©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6897-6905 (2015) repeat beyond normal levels and the other had a deletion in exon 1 of the FMR1 gene, which was confirmed by sequencing. Both probands were over 18 years old, which demonstrates the late diagnosis of the condition in these individuals and reinforces the need to implement effective programs for early diagnosis of FXS in the state of Maranhão. We found that FXS might be transmitted in the families of the two individuals bearing the mutation, and that it is important to understand the mutation dynamics to provide better counseling to the family members of these two individuals.

Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome

“…8 Around 1-2% of all children with developmental delay are found to have FXS caused by a CGG expansion. 4 However, others disease-causing FMR1 variants have also been reported, including large gene deletions, 5′UTR or exon 1 deletions associated or not with a full FMR1 CGG expansion in the mother, [9][10][11][12][13][14][15] as well as a very small number of single-nucleotide variants (SNVs) in the FMR1 coding regions. Direct sequencing of FMR1 was not frequently carried out, and only a few groups have screened for variants in FMR1 coding regions in clinically relevant cohorts presenting 16,17 or not [18][19][20] alterations of FMRP at the protein level.…”

“…Other FMR1 point variations reported in individuals with ID and in the general population Whereas it is clear that CGG-repeat expansion in the FMR1 promoter is by far the most frequent cause of FXS, other types of variations, particularly FMR1 deletions, have also been reported in FXS. 9 Deletions of the entire gene or of its first exon, 10-12 associated or not with full FMR1 CGG expansion in the mother, [13][14][15] have been found by conventional CGG expansion testing or by microarray analysis. Since 1992, screening for variations in the FMR1 coding sequence, performed in Fragile-X-evocative or nonspecific ID patients without expanded CGG-repeats and subsequent methylation, [16][17][18][19][20]22,23 has led to the identification of several rare intragenic non-synonymous variations within the FMR1 locus (Table 3 and Supplementary Table S2).…”

Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome

“… 4 FXS has an estimated incidence of 1 in 4,000 men and 1 in 8,000 women without known incidence in Brazil. 5 This neurodevelopmental disorder is characterized by a broad spectrum of behaviors, such as delayed neuropsychomotor development (ADNPM), anxiety, aggression, self-injury, attention deficit disorder, social withdrawal, and physical comorbidities, such as facial dysmorphisms, macroorchidism, otitis, and seizures, resulting in a large phenotypic heterogeneity across the FXS population. 6 The syndrome is caused by the loss of fragile X mental retardation protein (FMRP), a consequence of the full mutation (FM), more than 200 cytosine-guanine-guanine (CGG) repeats in the 5′ untranslated region of the fragile X mental retardation 1 ( FMR1 ) gene (OMIM# 309550) that leads to hypermethylation of the promoter region, and consequently the absence of the FMRP.…”