FXS FMR1

Disease ID
FXS, FXTAS, POF1
Gene ID
FMR1
Updated
Feb 5, 2025
v2.2.1

Disease

Name
Fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency FXPOI/POF1
Inheritance
X-linked dominant
Description
A genetic syndrome caused by mutations in the FMR1 gene which is responsible for the expression of the fragile X mental retardation 1 protein. This protein participates in neural development. This syndrome is manifested with mental, emotional, behavioral, physical, and learning disabilities.; Any primary ovarian failure in which the cause of the disease is a mutation in the FMR1 gene.; Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia1,2,3 .
Prevalence
14 100,000
Incidence of full mutation in males 19/100,000; prevalence 14/100,0004 . Female prevalence 9/100,0005 . Known carrier frequency is approximately 300-500/100,000 but detected was 11/100,0006 . FXS prevalence 1:7000 males, 1:11,000 females; FX premutation carriers 1:290-855 males, 1:148-300 females7 . Found worldwide4 . In Thailand, 1 in 600 women carry a premutation, and 1 in 400 carry a 'gray zone' allele8 .
Age of Onset(Typical)Years0  781  65
Age of Onset Details
Typical: FXS 1 to 'first several years of life', FXTAS 60-654 ; Range: 09 - 7810 ; detailed description of typical symptom onset and diagnosis available from Arnold et al7 .

Locus

Details
Intermediate or 'gray zone' occur at 45-54 alleles and may be unstable enough to expand into the premutation range, as well as associate with parkinsonism11,4 . FXTAS/POI occurs at 55-200 repeats, FXS >200, late onset; AGG and CTG interruptions documented4,12 .
Mechanism
LoF/GoF
Loss of function via transcriptional silencing in FXS, RNA gain of function in FXTAS/FXPOI13,14 .
Year
199215 ; causative gene discovered in 199116
Gene Strand

Alleles

Ref. Motif
CGG
Pathogenic (ref.)
CGG
Pathogenic (gene)
CGG
BenignIntermediatePathogenicUnits5  4445  200201  2,000

gnomAD

References

Direct supporting references for info on this page.

1
Ontology Lookup Service (OLS)
mondo:0010383
2
Ontology Lookup Service (OLS)
mondo:0010706
3
Ontology Lookup Service (OLS)
mondo:0010382
4
FMR1 Disorders
Jessica Ezzell,Hunter, Elizabeth,Berry-Kravis, Heather,Hipp, Peter K.,Todd
GeneReviews® · 1993-01-01
genereviews:NBK1384
5
Epidemiology of fragile X syndrome: a systematic review and meta-analysis.
Jessica,Hunter, Oliver,Rivero-Arias, Angel,Angelov, Edward,Kim, Iain,Fotheringham, Jose,Leal
American journal of medical genetics. Part A · 2014-04-03
pmid:24700618
6
Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.
Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti
American journal of human genetics · 2017-11-02
pmid:29100084
8
Population-based FMR1 carrier screening among reproductive women.
Quratul,Ain, Ye Hyun,Hwang, Daryl,Yeung, Pacharee,Panpaprai, Wiwat,Iamurairat, Wiboon,Chutimongkonkul, Objoon,Trachoo, Flora,Tassone, Poonnada,Jiraanont
Journal of assisted reproduction and genetics · 2024-09-25
pmid:39320553
10
CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS).
Flora,Tassone, John,Adams, Elizabeth M,Berry-Kravis, Susannah S,Cohen, Alfredo,Brusco, Maureen A,Leehey, Lexin,Li, Randi J,Hagerman, Paul J,Hagerman
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2007-06-05
pmid:17427188
11
Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.
Deborah A,Hall, Sukriti,Nag, Bichun,Ouyang, David A,Bennett, Yuanqing,Liu, Aisha,Ali, Lili,Zhou, Elizabeth,Berry-Kravis
Movement disorders : official journal of the Movement Disorder Society · 2020-05-28
pmid:32463542
12
Detecting AGG Interruptions in Females With a FMR1 Premutation by Long-Read Single-Molecule Sequencing: A 1 Year Clinical Experience.
Simon,Ardui, Valerie,Race, Thomy,de Ravel, Hilde,Van Esch, Koenraad,Devriendt, Gert,Matthijs, Joris R,Vermeesch
Frontiers in genetics · 2018-05-16
pmid:29868108
13
Diseases of unstable repeat expansion: mechanisms and common principles.
Jennifer R,Gatchel, Huda Y,Zoghbi
Nature reviews. Genetics · 2005-10-01
pmid:16205714
14
Clinical and neuroimaging review of triplet repeat diseases.
Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe
Japanese journal of radiology · 2022-09-28
pmid:36169768
15
Molecular studies of the fragile X syndrome.
S J,Knight, M C,Hirst, A,Roche, Z,Christodoulou, S M,Huson, R,Winter, M,Fitchett, M J,McKinley, R H,Lindenbaum, Y,Nakahori
American journal of medical genetics
pmid:1605194
16
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.
A J,Verkerk, M,Pieretti, J S,Sutcliffe, Y H,Fu, D P,Kuhl, A,Pizzuti, O,Reiner, S,Richards, M F,Victoria, F P,Zhang
Cell · 1991-05-31
pmid:1710175

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)