Cargando…

Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador

Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability and the second most common cause of intellectual disability of genetic etiology. This complex neurodevelopmental disorder is caused by an alteration in the CGG trinucleotide expansion in fragile X mental retardat...

Descripción completa

Detalles Bibliográficos
Autores principales: Pozo-Palacios, Juan, Llamos-Paneque, Arianne, Rivas, Christian, Onofre, Emily, López-Cáceres, Andrea, Villareal, Jenniffer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710471/
https://www.ncbi.nlm.nih.gov/pubmed/34966298
http://dx.doi.org/10.3389/fpsyt.2021.716311
_version_ 1784623161035194368
author Pozo-Palacios, Juan
Llamos-Paneque, Arianne
Rivas, Christian
Onofre, Emily
López-Cáceres, Andrea
Villareal, Jenniffer
author_facet Pozo-Palacios, Juan
Llamos-Paneque, Arianne
Rivas, Christian
Onofre, Emily
López-Cáceres, Andrea
Villareal, Jenniffer
author_sort Pozo-Palacios, Juan
collection PubMed
description Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability and the second most common cause of intellectual disability of genetic etiology. This complex neurodevelopmental disorder is caused by an alteration in the CGG trinucleotide expansion in fragile X mental retardation gene 1 (FMR1) leading to gene silencing and the subsequent loss of its product: fragile X mental retardation protein 1 (FMRP). Molecular diagnosis is based on polymerase chain reaction (PCR) screening followed by Southern blotting (SB) or Triplet primer-PCR (TP-PCR) to determine the number of CGG repeats in the FMR1 gene. We performed, for the first time, screening in 247 Ecuadorian male individuals with clinical criteria to discard FXS. Analysis was carried out by the Genetics Service of the Hospital de Especialidades No. 1 de las Fuerzas Armadas (HE-1), Ecuador. The analysis was performed using endpoint PCR for CGG fragment expansion analysis of the FMR1 gene. Twenty-two affected males were identified as potentially carrying the full mutation in FMR1 and thus diagnosed with FXS that is 8.1% of the sample studied. The average age at diagnosis of the positive cases was 13 years of age, with most cases from the geographical area of Pichincha (63.63%). We confirmed the familial nature of the disease in four cases. The range of CGG variation in the population was 12–43 and followed a modal distribution of 27 repeats. Our results were similar to those reported in the literature; however, since it was not possible to differentiate between premutation and mutation cases, we can only establish a molecular screening approach to identify an expanded CGG repeat, which makes it necessary to generate national strategies to optimize molecular tests and establish proper protocols for the diagnosis, management, and follow-up of patients, families, and communities at risk of presenting FXS.
format Online
Article
Text
id pubmed-8710471
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87104712021-12-28 Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador Pozo-Palacios, Juan Llamos-Paneque, Arianne Rivas, Christian Onofre, Emily López-Cáceres, Andrea Villareal, Jenniffer Front Psychiatry Psychiatry Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability and the second most common cause of intellectual disability of genetic etiology. This complex neurodevelopmental disorder is caused by an alteration in the CGG trinucleotide expansion in fragile X mental retardation gene 1 (FMR1) leading to gene silencing and the subsequent loss of its product: fragile X mental retardation protein 1 (FMRP). Molecular diagnosis is based on polymerase chain reaction (PCR) screening followed by Southern blotting (SB) or Triplet primer-PCR (TP-PCR) to determine the number of CGG repeats in the FMR1 gene. We performed, for the first time, screening in 247 Ecuadorian male individuals with clinical criteria to discard FXS. Analysis was carried out by the Genetics Service of the Hospital de Especialidades No. 1 de las Fuerzas Armadas (HE-1), Ecuador. The analysis was performed using endpoint PCR for CGG fragment expansion analysis of the FMR1 gene. Twenty-two affected males were identified as potentially carrying the full mutation in FMR1 and thus diagnosed with FXS that is 8.1% of the sample studied. The average age at diagnosis of the positive cases was 13 years of age, with most cases from the geographical area of Pichincha (63.63%). We confirmed the familial nature of the disease in four cases. The range of CGG variation in the population was 12–43 and followed a modal distribution of 27 repeats. Our results were similar to those reported in the literature; however, since it was not possible to differentiate between premutation and mutation cases, we can only establish a molecular screening approach to identify an expanded CGG repeat, which makes it necessary to generate national strategies to optimize molecular tests and establish proper protocols for the diagnosis, management, and follow-up of patients, families, and communities at risk of presenting FXS. Frontiers Media S.A. 2021-12-13 /pmc/articles/PMC8710471/ /pubmed/34966298 http://dx.doi.org/10.3389/fpsyt.2021.716311 Text en Copyright © 2021 Pozo-Palacios, Llamos-Paneque, Rivas, Onofre, López-Cáceres and Villareal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Pozo-Palacios, Juan
Llamos-Paneque, Arianne
Rivas, Christian
Onofre, Emily
López-Cáceres, Andrea
Villareal, Jenniffer
Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title_full Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title_fullStr Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title_full_unstemmed Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title_short Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador
title_sort experiences of the molecular diagnosis of fragile x syndrome in ecuador
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710471/
https://www.ncbi.nlm.nih.gov/pubmed/34966298
http://dx.doi.org/10.3389/fpsyt.2021.716311
work_keys_str_mv AT pozopalaciosjuan experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador
AT llamospanequearianne experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador
AT rivaschristian experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador
AT onofreemily experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador
AT lopezcaceresandrea experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador
AT villarealjenniffer experiencesofthemoleculardiagnosisoffragilexsyndromeinecuador