2016
DOI: 10.1002/ajmg.a.37954
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Partially methylated alleles, microdeletion, and tissue mosaicism in a fragile X male with tremor and ataxia at 30 years of age: A case report

Abstract: CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid autism. Unmethylated premutation (55-199 repeats) and FM alleles have been associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33-year-old male with FXS, with white matter changes and progressive deterior… Show more

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Cited by 22 publications
(26 citation statements)
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“…Patients with methylation mosaicism may exhibit a milder phenotype than full mutation patients with non-methylation mosaicism, the extreme example being males with full mutation expansions that are completely unmethylated, and who typically have mild cognitive impairment (but are at risk of premutation phenotypes such as FXTAS). 38 Interestingly, males with unmethylated full mutation are more likely to have a CGG repeat size in the range 200 to 400, consistent with the threshold for stable methylation of full mutation alleles being greater than 400, rather than over 200, as previously documented. 19 Females are, in a sense, all methylation mosaics because the FMR1 locus is sensitive to X-inactivation, such that normal levels of FMR1 promoter methylation are about 50%, and females with full mutation expansions typically have methylation levels closer to 75%.…”
Section: Mosaicism and Fxssupporting
confidence: 79%
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“…Patients with methylation mosaicism may exhibit a milder phenotype than full mutation patients with non-methylation mosaicism, the extreme example being males with full mutation expansions that are completely unmethylated, and who typically have mild cognitive impairment (but are at risk of premutation phenotypes such as FXTAS). 38 Interestingly, males with unmethylated full mutation are more likely to have a CGG repeat size in the range 200 to 400, consistent with the threshold for stable methylation of full mutation alleles being greater than 400, rather than over 200, as previously documented. 19 Females are, in a sense, all methylation mosaics because the FMR1 locus is sensitive to X-inactivation, such that normal levels of FMR1 promoter methylation are about 50%, and females with full mutation expansions typically have methylation levels closer to 75%.…”
Section: Mosaicism and Fxssupporting
confidence: 79%
“…Methylation mosaicism describes the presence, in an individual with a full mutation, of a population of cells that are methylated at the FMR1 locus and a second population of cells that are unmethylated. Patients with methylation mosaicism may exhibit a milder phenotype than full mutation patients with non‐methylation mosaicism, the extreme example being males with full mutation expansions that are completely unmethylated, and who typically have mild cognitive impairment (but are at risk of premutation phenotypes such as FXTAS) . Interestingly, males with unmethylated full mutation are more likely to have a CGG repeat size in the range 200 to 400, consistent with the threshold for stable methylation of full mutation alleles being greater than 400, rather than over 200, as previously documented …”
Section: Mosaicism and Fxssupporting
confidence: 73%
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“…While significant increases in FMR1 mRNA were reported in blood from all three cases, CGG size testing in other peripheral tissues identified PM/FM mosaicism for one of these [ 18 ]. More recently, we have described tissue mosaicism for FM methylation and a microdeletion proximal to the CGG repeat in a 33 year old male with clinical and MRI findings consistent with FXTAS, which is the youngest case reported to date of probable FXTAS [ 19 ].…”
Section: Introductionmentioning
confidence: 99%