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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Bibliographic Details
Published in:International journal of molecular sciences 2023-05, Vol.24 (11), p.9206
Main Authors: 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
Format: Article
Language:English
Subjects:
Alleles
Ataxia
Autism
Care and treatment
Cell culture
Diagnosis
DNA Methylation
Fragile X Mental Retardation Protein - genetics
Fragile X Mental Retardation Protein - metabolism
Fragile X syndrome
Fragile X Syndrome - diagnosis
Fragile X Syndrome - genetics
Gene mapping
Gene Silencing
Genes
Genetic engineering
Genomes
Genomics
Genotype & phenotype
Humans
Intellectual disabilities
Ions
Methylation
Mosaicism
Mutation
New technology
Polymerase chain reaction
Proteins
Review
Trinucleotide Repeats
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Summary: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 ( ) 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24119206