Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome

Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability (ID) and single gene cause of autism. Although most patients with FXS and the full mutation (FM) have complete methylation of the fragile X messenger ribonucleoprotein 1 ( ) gene, some have mosaicism in methylation an...

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Bibliographic Details
Published in:Genes 2024-03, Vol.15 (3), p.331
Main Authors: Tak, YeEun, Schneider, Andrea, Santos, Ellery, Randol, Jamie Leah, Tassone, Flora, Hagerman, Paul, Hagerman, Randi J
Format: Article
Language:English
Subjects:
Alleles
Ataxia
Autism
Cognitive ability
Development and progression
DNA methylation
DNA Methylation - genetics
Females
FMR1 protein
Fragile X Mental Retardation Protein - genetics
Fragile X syndrome
Fragile X Syndrome - complications
Fragile X Syndrome - genetics
Gene expression
Genes
Genetic aspects
Humans
Intellectual disabilities
Male
Males
Methylation
Mosaicism
mRNA
Mutation
Phenotypes
Primidone
Review
RNA
Toxicity
Tremor
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Description
Summary:Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability (ID) and single gene cause of autism. Although most patients with FXS and the full mutation (FM) have complete methylation of the fragile X messenger ribonucleoprotein 1 ( ) gene, some have mosaicism in methylation and/or CGG repeat size, and few have completely unmethylated FM alleles. Those with a complete lack of methylation are rare, with little literature about the cognitive and behavioral phenotypes of these individuals. A review of past literature was conducted regarding individuals with unmethylated and mosaic FM. We report three patients with an unmethylated FM alleles without any behavioral or cognitive deficits. This is an unusual presentation for men with FM as most patients with an unmethylated FM and no behavioral phenotypes do not receive fragile X DNA testing or a diagnosis of FXS. Our cases showed that mosaic males with unmethylated FM alleles may lack behavioral phenotypes due to the presence of smaller alleles producing the protein (FMRP). However, these individuals could be at a higher risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) due to the increased expression of mRNA, similar to those who only have a premutation.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes15030331