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 (<i>FMR1</i>) gene, some have mosai...
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MDPI AG
2024-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/15/3/331 |
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| author | YeEun Tak Andrea Schneider Ellery Santos Jamie Leah Randol Flora Tassone Paul Hagerman Randi J. Hagerman |
| author_facet | YeEun Tak Andrea Schneider Ellery Santos Jamie Leah Randol Flora Tassone Paul Hagerman Randi J. Hagerman |
| author_sort | YeEun Tak |
| collection | DOAJ |
| description | 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 (<i>FMR1</i>) 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 <i>FMR1</i> FM. We report three patients with an unmethylated FM <i>FMR1</i> 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 <i>FMR1</i> FM alleles may lack behavioral phenotypes due to the presence of smaller alleles producing the <i>FMR1</i> 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. |
| first_indexed | 2024-04-24T18:15:05Z |
| format | Article |
| id | doaj.art-ca10ad7ea7104b64869fded58d3fbdca |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-04-24T18:15:05Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ca10ad7ea7104b64869fded58d3fbdca2024-03-27T13:43:06ZengMDPI AGGenes2073-44252024-03-0115333110.3390/genes15030331Unmethylated Mosaic Full Mutation Males without Fragile X SyndromeYeEun Tak0Andrea Schneider1Ellery Santos2Jamie Leah Randol3Flora Tassone4Paul Hagerman5Randi J. Hagerman6Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA 95616, USADepartment of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA 95616, USADepartment of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA 95616, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA 95616, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA 95616, USAFragile 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 (<i>FMR1</i>) 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 <i>FMR1</i> FM. We report three patients with an unmethylated FM <i>FMR1</i> 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 <i>FMR1</i> FM alleles may lack behavioral phenotypes due to the presence of smaller alleles producing the <i>FMR1</i> 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.https://www.mdpi.com/2073-4425/15/3/331unmethylated full mutationfragile X premutationfragile X mosaicismfragile X syndromefragile X premutation-associated conditions |
| spellingShingle | YeEun Tak Andrea Schneider Ellery Santos Jamie Leah Randol Flora Tassone Paul Hagerman Randi J. Hagerman Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome Genes unmethylated full mutation fragile X premutation fragile X mosaicism fragile X syndrome fragile X premutation-associated conditions |
| title | Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome |
| title_full | Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome |
| title_fullStr | Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome |
| title_full_unstemmed | Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome |
| title_short | Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome |
| title_sort | unmethylated mosaic full mutation males without fragile x syndrome |
| topic | unmethylated full mutation fragile X premutation fragile X mosaicism fragile X syndrome fragile X premutation-associated conditions |
| url | https://www.mdpi.com/2073-4425/15/3/331 |
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