FRDA FXN

1/50,000^2,3: Known carrier frequency 1000/100,000; observed 421/100,000. Most common inherited ataxia in Europe, the Middle East, India, and North Africa; not documented in Southeast Asia, in sub-Saharan Africa, or among Native Americans⁴.

Age of Onset Details

Typical: 10-15; Range: 2-80⁴.

Locus

hg19

chr9:71652202-71652220

hg38

chr9:69037286-69037304

t2t

chr9:81210843-81210861

Details

96% of FA patients have biallelic GAA expansions in intron 1 (compared to compound heterozygous with another mutation type), in which the reference allele is conventionally 5-33 repeats⁴. Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated⁴. The expanded repeats can interrupted either with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes⁵. Allele size is correlated with disease severity and inversely correlated to age of onset, and expansions can reach 1700 repeats⁶.

Mechanism

LoF

Loss of function via transcriptional silencing^7,8.

Year

1996⁹

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Pathogenic (ref.)

GAA

Pathogenic (gene)

AAG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0100340

omim:229300

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

Friedreich Ataxia

Sanjay I.,Bidichandani, Martin B.,Delatycki, Marek,Napierala, Antoine,Duquette

GeneReviews® · 1993-01-01

genereviews:NBK1281

Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia.

D O,McDaniel, B,Keats, V V,Vedanarayanan, S H,Subramony

Movement disorders : official journal of the Movement Disorder Society · 2001-11-01

pmid:11748752

Clinical and genetic abnormalities in patients with Friedreich's ataxia.

A,Dürr, M,Cossee, Y,Agid, V,Campuzano, C,Mignard, C,Penet, J L,Mandel, A,Brice, M,Koenig

The New England journal of medicine · 1996-10-17

pmid:8815938

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

Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.

V,Campuzano, L,Montermini, M D,Moltò, L,Pianese, M,Cossée, F,Cavalcanti, E,Monros, F,Rodius, F,Duclos, A,Monticelli, F,Zara, J,Cañizares, H,Koutnikova, S I,Bidichandani, C,Gellera, A,Brice, P,Trouillas, G,De Michele, A,Filla, R,De Frutos, F,Palau, P I,Patel, S,Di Donato, J L,Mandel, S,Cocozza, M,Koenig, M,Pandolfo

Science (New York, N.Y.) · 1996-03-08

pmid:8596916

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)

Assessment of the Clinical Interactions of GAA Repeat Expansions in

Brandon J,Gerhart, David,Pellerin, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Gabriel,Matos-Rodrigues, Andre,Nussenzweig, Karen,Usdin, Courtney C,Park, Jill S,Napierala, David R,Lynch, Marek,Napierala

Neurology. Genetics · 2024-11-20

pmid:39574782

Screening for SCA27B, CANVAS and other repeat expansion disorders in Greek patients with late-onset cerebellar ataxia suggests a need to update current diagnostic algorithms.

Georgios,Koutsis, Chrisoula,Kartanou, Zoi,Kontogeorgiou, Chrysoula,Koniari, Alexandros,Mitrousias, David,Pellerin, Marie-Jose,Dicaire, Pablo,Iruzubieta, Matt C,Danzi, Konstantinos,Athanassopoulos, Nikolaos,Ragazos, Maria,Stamelou, Michail,Rentzos, Evangelos,Anagnostou, Stephan,Zuchner, Bernard,Brais, Henry,Houlden, Marios,Panas, Leonidas,Stefanis, Georgia,Karadima

Journal of the neurological sciences · 2024-11-15

pmid:39571249

Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters.

Sara,Petrillo, Alessia,Perna, Andrea,Quatrana, Gabriella,Silvestri, Enrico,Bertini, Fiorella,Piemonte, Massimo,Santoro

International journal of molecular sciences · 2024-10-29

pmid:39519164

Uniparental IsoDisomy: a case study on a new mechanism of Friedreich ataxia.

Brian,Sperelakis-Beedham, Cyril,Gitiaux, Marine,Rajaoba, Maryse,Magen, Nicolas,Derive, Jerome,Chansard, Jean-Madeleine,de Sainte Agathe, Marie-Laure,Maurin, Zahra,Assouline, Christine,Barnerias, Isabelle,Desguerre, Julie,Steffann, Giulia,Barcia

European journal of human genetics : EJHG · 2024-11-04

pmid:39496895

Case Report of Friedreich's Ataxia and ALG1-Related Biochemical Abnormalities in a Patient With Progressive Spastic Paraplegia.

Aisling,Quinlan, Lance,Rodan, Elizabeth,Barkoudah, Amy,Tam, Afshin,Saffari, Ibrahim,Shammas, Wasantha,Ranatunga, Eva,Morava-Kozicz, Devin,Oglesbee, Gerald,Berry, Darius,Ebrahimi-Fakhari, Siddharth,Srivastava

American journal of medical genetics. Part A · 2024-09-26

pmid:39324476

Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia.

Daniela,Scarabino, Liana,Veneziano, Suran,Nethisinghe, Elide,Mantuano, Alessia,Fiore, Giulia,Granata, Nita,Solanky, Ginevra,Zanni, Francesca,Cavalcanti, Rosa Maria,Corbo, Paola,Giunti

Movement disorders : official journal of the Movement Disorder Society · 2024-09-05

pmid:39235665

Nerve ultrasound in CANVAS-spectrum disease: Reduced nerve size distinguishes genetically confirmed CANVAS from other axonal polyneuropathies.

Alessandro,Salvalaggio, Mario,Cacciavillani, Benedetta,Tierro, Daniele,Coraci, Riccardo,Currò, Moreno,Ferrarini, Elena,Pegoraro, Luca,Bello, Gian Maria,Fabrizi, Alessandro,Filla, Luca,Padua, Fiore,Manganelli, Andrea,Cortese, Chiara,Briani

Journal of the peripheral nervous system : JPNS · 2024-09-02

pmid:39219417

DNA Base Damage Repair Crosstalks with Chromatin Structures to Contract Expanded GAA Repeats in Friedreich's Ataxia.

Yanhao,Lai, Nicole,Diaz, Rhyisa,Armbrister, Irina,Agoulnik, Yuan,Liu

Biomolecules · 2024-07-08

pmid:39062522

Generation of genetically modified Friedreich's ataxia induced pluripotent stem cell lines and isogenic control lines carrying an inducible neurogenin-2 expression cassette.

Sara,Miellet, Marnie,Maddock, Jill S,Napierala, Marek,Napierala, Mirella,Dottori

Stem cell research · 2024-06-21

pmid:38936158