FXS FMR1

A genetic syndrome caused by mutations in the FMR1 gene which is responsible for the expression of the fragile X messenger ribonucleoprotein 1 (FMR1) 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 ataxia^1,2,3.

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 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

hg19

chrX:146993567-146993629

hg38

chrX:147912049-147912111

t2t

chrX:146176677-146176769

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 parkinsonism^11,4. FXTAS/POI occurs at 55-200 repeats, FXS >200, late onset; AGG and CTG interruptions documented^4,12. Women with the premutation have been reported showing episodic memory deficits, similar to those seen in AD¹³.

Mechanism

LoF/GoF

Loss of function via transcriptional silencing in FXS, RNA gain of function in FXTAS/FXPOI^14,15. PRKGG appears to modulate neurotoxicity¹⁶.

Year

1992¹⁷; causative gene discovered in 1991¹⁸

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CGG

Pathogenic (ref.)

CGG

Pathogenic (gene)

CGG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010383

Ontology Lookup Service (OLS)

mondo:0010706

Ontology Lookup Service (OLS)

mondo:0010382

genereviews:NBK1384

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

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

isbn:978-3-031-66932-3

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

UpToDate

url:https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents

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

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

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

Cognitive dysfunction in women with the

Jessica,Klusek, Jillian,Gierman, Amanda J,Fairchild, Andreana M,Benitez, Elizabeth,Berry-Kravis, Marsha R,Mailick

Journal of Alzheimer's disease : JAD · 2026-01-20

pmid:41555826

Diseases of unstable repeat expansion: mechanisms and common principles.

Jennifer R,Gatchel, Huda Y,Zoghbi

Nature reviews. Genetics · 2005-10-01

pmid:16205714

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

Integrative transcriptome-wide association analyses reveal PRKCG-linked GABAergic dysfunction in Fragile X-associated tremor/ataxia syndrome.

Yulin,Jin, Yiqu,Cao, Wenjing,Ma, Ronghua,Li, Yujing,Li, Yunhee,Kang, Jing,Huang, Michael P,Epstein, Xiangxue,Guo, Junghwa,Lim, Natalia,Rivera, Ying,Zhou, Zhexing,Wen, Emily G,Allen, Peng,Jin

Nature communications · 2026-01-08

pmid:41507195

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

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)

Short tandem repeat expansions in patients with neurodegenerative dementia.

Yuan,Zhu, Xuewen,Xiao, Yiliang,Liu, Zheng,Wang, Tengfei,Luo, Tianyan,Xu, Qijie,Yang, Xiaoli,Hao, Cong,Zhang, Sizhe,Zhang, Shilin,Luo, Yafang,Zhou, Xinxin,Liao, Yun,Tian, Ling,Weng, Liangjuan,Fang, Beisha,Tang, Bin,Jiao, Jinchen,Li, Lu,Shen

EBioMedicine · 2026-02-26

pmid:41762523

Protective role of PASH-1 in CGG repeat-driven RNA and protein toxicity in FXTAS.

Tsung-Yuan,Hsu, Hsin-Ya,Yang, Lin-Shiang,Hsieh, Kuan-Yen,Chen, Guang-Yuh,Chiou, Albert Y,Chen, Jay,Shieh, Noelle D,L'Etoile, Paul J,Hagerman, Bi-Tzen,Juang

iScience · 2026-01-27

pmid:41717020

Performance Evaluation of PacBio PureTarget for Multiple Short Tandem Repeat Expansion Detection.

Eunju,Yeom, Yu Jin,Park, Saeam,Shin, Seung-Tae,Lee, Mi-Kyeong,Lee, Kyoung-Ryul,Lee, Dongju,Won, Jong Rak,Choi

Annals of laboratory medicine · 2026-02-12

pmid:41672630

Genetic diagnosis of three intellectually disabled individuals in a pedigree and insights into fragile X syndrome diagnosis.

Jianmei,Huang, Bing,Kang, Xiaoliang,Xia, Zhenglong,Guo, Yibing,Lv, Wenke,Yang, Chenyang,Wang, Jinming,Wang, Shixiu,Liao

Frontiers in neuroscience · 2026-01-21

pmid:41648852

Metabolic reprogramming during human neuron differentiation indicates glutaminase as a key determinant in Fragile X syndrome.

Sneha,Shah, Daniel,Barnes, Botao,Liu, Tenzin,Tseyang, Thang,Do, Jodi L,Bubenik, Suna,Jung, Mina N,Anadolu, Maria P,Ivshina, Verónica,Martínez-Cerdeño, Elizabeth,Berry-Kravis, Maurice S,Swanson, Jessica B,Spinelli, Joel D,Richter

Cell reports · 2026-01-19

pmid:41557506

Screening of CGG Trinucleotide Repeats Within

Abdullah Al,Noman, Abdullah Al,Saba, Maisha,Adiba, Molie,Rahman, Mohammad,Sayem, A H M Nurun,Nabi, Tahirah,Yasmin

Journal of the Korean Academy of Child and Adolescent Psychiatry · 2025-10-20

pmid:41523206

Long-read genome sequencing enhances diagnostics of pediatric neurological disorders.

Marlene,Ek, Malin,Kvarnung, Esmee,Ten Berk de Boer, Linnéa,La Fleur, Lena,Ljöstad, Anna,Lyander, Søren Lejsted,Faergeman, Simon Opstrup,Drue, Håkan,Thonberg, Ann,Nordgren, Maria Johansson,Soller, Valtteri,Wirta, Jesper,Eisfeldt, Anna,Lindstrand

Genome medicine · 2026-01-09

pmid:41514368

Molecular Repositioning of Celecoxib as a Neurotherapeutic Agent in Fragile X‑Associated Tremor/Ataxia Syndrome (FXTAS).

Soumalya,Das, Aditi Pramod,Kumari, Krishna,Singh, Sakshi,Shukla, Shubhi,Khandelwal, Amit,Kumar

ACS pharmacology & translational science · 2025-11-05

pmid:41409170

Detection of FMR1 CGG Repeat Expansions Using Buccal Swab and Blood Samples of Children With Intellectual Disability in A Resource-Limited Country.

Siti F,Aulia, Mentari,Amir, Intan,Razari, Kinasih,Prayuni, Wan,Nedra, Ndaru A,Damayanti, Nurmayani,Irwandi, Ahmad,Utomo, Vivienne J,Tan, Samuel S,Chong, Sultana M H,Faradz

Journal, genetic engineering & biotechnology · 2025-10-02

pmid:41386846