FRDA FXN

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty¹.

Prevalence

1 50,000

1/50,000^1,2: 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 Americans³.

Age of Onset Details

Typical: 10-15; Range: 2-80³.

Locus

hg19

chr9:71652202-71652220

hg38

chr9:69037286-69037304

t2t

chr9:81210834-81210861

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 repeats³. Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated³. The expanded repeats can interrupted either with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes⁴. Allele size is correlated with disease severity and inversely correlated to age of onset, and expansions can reach 1700 repeats⁵.

Mechanism

LoF

Loss of function via transcriptional silencing^6,7.

Year

1996⁸

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Pathogenic (ref.)

GAA

Pathogenic (gene)

AAG

gnomAD

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

References

Direct supporting references for info on this page.

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

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)

Early experience on omaveloxolone in adult patients with Friedreich's ataxia: a real-world observational study.

Salvatore Maria,Lima, Marta,Caltagirone, Christian,Messina, Umberto,Quartetti, Nicasio,Rini, Flora,D'Amico, Filippo,Brighina, Vincenzo,Di Stefano

Journal of neurology · 2025-11-01

pmid:41176519

Development of an AAV-Based Gene Therapy for the Ocular Phenotype of Friedreich's Ataxia.

Heyu,Tang, Siddhant,Gupte, Emily,Xu, Kaitlyn R,Calabro, Hannah,Friend, Sean M,Crosson, Diego,Fajardo, Zachary,Kostamo, Hangning,Zhang, James J,Peterson, Fangyu,Lin, Zbynek,Kozmik, Cathleen M,Lutz, Sanford L,Boye, Shannon E,Boye

Molecular therapy : the journal of the American Society of Gene Therapy · 2025-10-23

pmid:41137390

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia.

Mehdi,Benkirane, Cecilia,Marelli, Ariane,Choumert, Cyril,Goizet, Olivier,Patat, Claire,Ewenczyk, Mathieu,Anheim, André,Mégarbané, Lise,Larrieu, Cyril,Charlin, Fabienne,Ory-Magne, Annabelle,Chaussenot, Mélanie,Fradin, Claire,Guissart, Morgane,Pointaux, Mireille,Cossée, Marie-Claire,Vincent, Anne,Bergougnoux, Clément,Hersent, Corinne,Bareil, Agathe,Roubertie, Frédérique,Fluchère, Mathilde,Renaud, Laurent,Kremer, Christine,Tranchant, Shahram,Attarian, Sylvie,Odent, Vincent,Laugel, Ulrike,Walther-Louvier, Beatrice,Desnous, Eric,Bieth, Isabelle,Husson, Jean Phillipe,Azulay, François,Rivier, Bérénice,Doray, Alexandra,Durr, Safa,Aouinti, Nicolas,Molinari, Michel,Koenig

Genetics in medicine : official journal of the American College of Medical Genetics · 2025-09-23

pmid:41014100

Impact of age on neurofilament light chain in Friedreich ataxia: a 1-year longitudinal study.

Sara,Petrillo, Alessia,Mongelli, Anna,Castaldo, Lidia,Sarro, Samuele,Azzarelli, Riccardo,Ronco, Barbara,Castellotti, Cinzia,Gellera, Fiorella,Piemonte, Caterina,Mariotti

Brain communications · 2025-09-10

pmid:40994821

Friedreich's Ataxia in Colombia: A Population-Based Study of Incidence and Socioeconomic Determinants.

Cristian,Correa-Arrieta, Sandra,Castellar-Leones, Edicson,Ruiz-Ospina, Milena,Villamil-Osorio, Edna Julieth,Bobadilla-Quesada, Fernando,Ortiz-Corredor

Movement disorders : official journal of the Movement Disorder Society · 2025-09-19

pmid:40970480

Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing.

Hannes,Erdmann, Annalisa,Schaub, Morghan C,Lucas, Veronika,Scholz, Anna,Benet-Pages, Kerstin,Becker, Christine,Dineiger, Veronika,Mayer, Inga,van Buren, Eva,Breithausen, Karl,Akbari, Isabell,Cordts, Mayra,Sauer, Christine,Schneider, Rosanna,Krakowsky, Franziska,Schnabel, Konstanze,Dunker, Lena,Fabritius, Johannes,Gerb, Denis,Grabova, Ken,Möhwald, Marius,Näher, Karoline,Steinmetz, Franziska,Thiessen, Alexander,Jäck, Christiane,Schneider-Gold, Simone,Zittel, Christina,Petersen, Isolde,Schreyer, Larissa,Mämecke, Sibylle,Wilfling, Gilbert,Wunderlich, David,Brenner, Yorck,Hellenbroich, Kirsten,Muhle, Tessa,Huchtemann, Inga,Claus, Thomas,Klopstock, Michael,Strupp, Johannes,Levin, Günter,Höglinger, Doreen,Huppert, Sandra,Becker-Bense, Filipp,Filippopulos, Fabian,Kilpert, Elsa,Leitão, Sabine,Kaya, Christel,Depienne, Florian,Schöberl, Teresa,Neuhann, Elke,Holinski-Feder, Andreas,Zwergal, Angela,Abicht

Brain : a journal of neurology · 2025-09-03

pmid:40898875

Genetic and Phenotypic Variability in Siblings With Friedreich Ataxia.

Khashayar,Eshaghi, Prima H,Rao, Megan M,Shen, David R,Lynch

Neurology. Genetics · 2025-01-13

pmid:40880907

Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich's Ataxia-GAA Repeats.

Joohyun,Park, Claudia,Dufke, Zofia,Fleszar, Michael,Schlotterbek, Elena,Buena-Atienza, Lara G,Stühn, Caspar,Gross, Marc,Sturm, Stephan,Ossowski, Ludger,Schöls, Olaf,Riess, Tobias B,Haack

International journal of molecular sciences · 2025-05-22

pmid:40507780