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Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome
The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252420/ https://www.ncbi.nlm.nih.gov/pubmed/37298158 http://dx.doi.org/10.3390/ijms24119206 |
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author | Ciobanu, Cristian-Gabriel Nucă, Irina Popescu, Roxana Antoci, Lucian-Mihai Caba, Lavinia Ivanov, Anca Viorica Cojocaru, Karina-Alexandra Rusu, Cristina Mihai, Cosmin-Teodor Pânzaru, Monica-Cristina |
author_facet | Ciobanu, Cristian-Gabriel Nucă, Irina Popescu, Roxana Antoci, Lucian-Mihai Caba, Lavinia Ivanov, Anca Viorica Cojocaru, Karina-Alexandra Rusu, Cristina Mihai, Cosmin-Teodor Pânzaru, Monica-Cristina |
author_sort | Ciobanu, Cristian-Gabriel |
collection | PubMed |
description | The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice. |
format | Online Article Text |
id | pubmed-10252420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102524202023-06-10 Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome Ciobanu, Cristian-Gabriel Nucă, Irina Popescu, Roxana Antoci, Lucian-Mihai Caba, Lavinia Ivanov, Anca Viorica Cojocaru, Karina-Alexandra Rusu, Cristina Mihai, Cosmin-Teodor Pânzaru, Monica-Cristina Int J Mol Sci Review The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice. MDPI 2023-05-24 /pmc/articles/PMC10252420/ /pubmed/37298158 http://dx.doi.org/10.3390/ijms24119206 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ciobanu, Cristian-Gabriel Nucă, Irina Popescu, Roxana Antoci, Lucian-Mihai Caba, Lavinia Ivanov, Anca Viorica Cojocaru, Karina-Alexandra Rusu, Cristina Mihai, Cosmin-Teodor Pânzaru, Monica-Cristina Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title | Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title_full | Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title_fullStr | Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title_full_unstemmed | Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title_short | Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome |
title_sort | narrative review: update on the molecular diagnosis of fragile x syndrome |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252420/ https://www.ncbi.nlm.nih.gov/pubmed/37298158 http://dx.doi.org/10.3390/ijms24119206 |
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