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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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