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Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles

This study describes monozygotic (MZ) male twins with fragile X syndrome (FXS), mosaic for normal size (NS: <44 CGGs), premutation (PM: 55–199 CGG) and full mutation (FM alleles ≥ 200) alleles, with autism. At 4 years of age chromosomal microarray confirmed monozygosity with both twins showing an...

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Autores principales: Pandelache, Alison, Baker, Emma K, Aliaga, Solange M., Arpone, Marta, Forbes, Robin, Stark, Zornitza, Francis, David, Godler, David E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523498/
https://www.ncbi.nlm.nih.gov/pubmed/30959842
http://dx.doi.org/10.3390/genes10040279
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author Pandelache, Alison
Baker, Emma K
Aliaga, Solange M.
Arpone, Marta
Forbes, Robin
Stark, Zornitza
Francis, David
Godler, David E.
author_facet Pandelache, Alison
Baker, Emma K
Aliaga, Solange M.
Arpone, Marta
Forbes, Robin
Stark, Zornitza
Francis, David
Godler, David E.
author_sort Pandelache, Alison
collection PubMed
description This study describes monozygotic (MZ) male twins with fragile X syndrome (FXS), mosaic for normal size (NS: <44 CGGs), premutation (PM: 55–199 CGG) and full mutation (FM alleles ≥ 200) alleles, with autism. At 4 years of age chromosomal microarray confirmed monozygosity with both twins showing an XY sex complement. Normal size (30 CGG), PM (99 CGG) and FM (388–1632 CGGs) alleles were detected in Twin 1 (T1) by standard polymerase chain reaction (PCR) and Southern blot testing, while only PM (99 CGG) and FM (672–1025) alleles were identified in Twin 2 (T2). At ~5 years, T2 had greater intellectual impairments with a full scale IQ (FSIQ) of 55 and verbal IQ (VIQ) of 59, compared to FSIQ of 62 and VIQ of 78 for T1. This was consistent with the quantitative FMR1 methylation testing, revealing 10% higher methylation at 80% for T2; suggesting that less active unmethylated alleles were present in T2 as compared to T1. AmplideX methylation PCR also identified partial methylation, including an unmethylated NS allele in T2, undetected by standard testing. In conclusion, this report demonstrates significant differences in intellectual functioning between the MZ twins mosaic for NS, PM and FM alleles with partial FMR1 promoter methylation.
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spelling pubmed-65234982019-06-03 Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles Pandelache, Alison Baker, Emma K Aliaga, Solange M. Arpone, Marta Forbes, Robin Stark, Zornitza Francis, David Godler, David E. Genes (Basel) Article This study describes monozygotic (MZ) male twins with fragile X syndrome (FXS), mosaic for normal size (NS: <44 CGGs), premutation (PM: 55–199 CGG) and full mutation (FM alleles ≥ 200) alleles, with autism. At 4 years of age chromosomal microarray confirmed monozygosity with both twins showing an XY sex complement. Normal size (30 CGG), PM (99 CGG) and FM (388–1632 CGGs) alleles were detected in Twin 1 (T1) by standard polymerase chain reaction (PCR) and Southern blot testing, while only PM (99 CGG) and FM (672–1025) alleles were identified in Twin 2 (T2). At ~5 years, T2 had greater intellectual impairments with a full scale IQ (FSIQ) of 55 and verbal IQ (VIQ) of 59, compared to FSIQ of 62 and VIQ of 78 for T1. This was consistent with the quantitative FMR1 methylation testing, revealing 10% higher methylation at 80% for T2; suggesting that less active unmethylated alleles were present in T2 as compared to T1. AmplideX methylation PCR also identified partial methylation, including an unmethylated NS allele in T2, undetected by standard testing. In conclusion, this report demonstrates significant differences in intellectual functioning between the MZ twins mosaic for NS, PM and FM alleles with partial FMR1 promoter methylation. MDPI 2019-04-05 /pmc/articles/PMC6523498/ /pubmed/30959842 http://dx.doi.org/10.3390/genes10040279 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pandelache, Alison
Baker, Emma K
Aliaga, Solange M.
Arpone, Marta
Forbes, Robin
Stark, Zornitza
Francis, David
Godler, David E.
Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title_full Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title_fullStr Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title_full_unstemmed Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title_short Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles
title_sort clinical and molecular differences between 4-year-old monozygous male twins mosaic for normal, premutation and fragile x full mutation alleles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523498/
https://www.ncbi.nlm.nih.gov/pubmed/30959842
http://dx.doi.org/10.3390/genes10040279
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