SCA27B FGF14

Intermediate expansions 1-2% of population, but non-GAA-pure without relation to ataxia². Found in multiple ethnicities³; diagnosed patients in America, Brazil, Japan, Germany, Spain, Canada, France, Austria and Australia².

Age of Onset Details

Typical: 42-70; Range: 21-87^2,4.

Locus

hg19

chr13:102813927-102814076

hg38

chr13:102161577-102161726

t2t

chr13:101377640-101377789

Details

Higher repeat size is associated with earlier age of onset⁴. The 250-300 repeats range is linked to incomplete penetrance and >300 repeats with complete penetrance in some studies and resources^2,5,6. However, our thresholds are taken from suggestions made by Mohren et al upon evaluation of 169 cases and 802 controls; the authors propose lower thresholds based on pathogenic cases of shorter pure repeats⁶. Additionally, this study suggests that benign motifs may disrupt the formation of secondary structures in DNA/RNA, leading to reduced pathogenicity. Variation in flanking regions appear to correlate with repeat size^6,7. Intermediate alleles make pose as susceptibility factors or be associated with a phenotypic spectrum (multiple system atrophy)^6,8.

Mechanism

LoF

Reduced transcript 2⁹.

Year

2023¹⁰

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Benign (ref.)

GAAGGA, GAAGAAGAAGAAGCA, AAGGAG

Benign (gene)

CCTTCT, CTGCTTCTTCTTCTT, CCTTCT

Pathogenic (ref.)

GAA

Pathogenic (gene)

CTT

References

Direct supporting references for info on this page.

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2024-09-30

pmid:39349043

GAA-FGF14-Related Ataxia

David,Pellerin, Matt,Danzi, Mathilde,Renaud, Henry,Houlden, Matthis,Synofzik, Stephan,Zuchner, Bernard,Brais

GeneReviews® · 1993-01-01

genereviews:NBK599589

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

Widad,Abou Chaar, Anirudh N,Eranki, Hannah A,Stevens, Sonya L,Watson, Darice Y,Wong, Veronica S,Avila, Megan,Delfeld, Alexander J,Gary, Sanjukta,Tawde, Malia,Triebold, Marcello,Cherchi, Tao,Xie, Paul J,Lockhart, Melanie,Bahlo, David,Pellerin, Marie-Josée,Dicaire, Matt,Danzi, Stephan,Zuchner, Bernard C,Brais, Susan,Perlman, Margit,Burmeister, Henry,Paulson, Sharan,Srinivasan, Lawrence,Schut, Matthew,Bower, Khalaf,Bushara, Chuanhong,Liao, Vikram G,Shakkottai, John,Collins, H Brent,Clark, Soma,Das, Brent L,Fogel, Christopher M,Gomez

Annals of neurology · 2024-09-12

pmid:39263992

Intronic

David,Pellerin, Carlo,Wilke, Andreas,Traschütz, Sara,Nagy, Riccardo,Currò, Marie-Josée,Dicaire, Hector,Garcia-Moreno, Mathieu,Anheim, Thomas,Wirth, Jennifer,Faber, Dagmar,Timmann, Christel,Depienne, Dan,Rujescu, José,Gazulla, Mary M,Reilly, Paola,Giunti, Bernard,Brais, Henry,Houlden, Ludger,Schöls, Michael,Strupp, Andrea,Cortese, Matthis,Synofzik

Journal of neurology, neurosurgery, and psychiatry · 2024-01-11

pmid:37399286

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Lars,Mohren, Friedrich,Erdlenbruch, Elsa,Leitão, Fabian,Kilpert, G Sebastian,Hönes, Sabine,Kaya, Christopher,Schröder, Andreas,Thieme, Marc,Sturm, Joohyun,Park, Agatha,Schlüter, Montserrat,Ruiz, Moisés,Morales de la Prida, Carlos,Casasnovas, Kerstin,Becker, Ulla,Roggenbuck, Sonali,Pechlivanis, Frank J,Kaiser, Matthis,Synofzik, Thomas,Wirth, Mathieu,Anheim, Tobias B,Haack, Paul J,Lockhart, Karl-Heinz,Jöckel, Aurora,Pujol, Stephan,Klebe, Dagmar,Timmann, Christel,Depienne

Nature communications · 2024-09-03

pmid:39227614

A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus.

David,Pellerin, Giulia F,Del Gobbo, Madeline,Couse, Egor,Dolzhenko, Sathiji K,Nageshwaran, Warren A,Cheung, Isaac R L,Xu, Marie-Josée,Dicaire, Guinevere,Spurdens, Gabriel,Matos-Rodrigues, Igor,Stevanovski, Carolin K,Scriba, Adriana,Rebelo, Virginie,Roth, Marion,Wandzel, Céline,Bonnet, Catherine,Ashton, Aman,Agarwal, Cyril,Peter, Dan,Hasson, Nadejda M,Tsankova, Ken,Dewar, Phillipa J,Lamont, Nigel G,Laing, Mathilde,Renaud, Henry,Houlden, Matthis,Synofzik, Karen,Usdin, Andre,Nussenzweig, Marek,Napierala, Zhao,Chen, Hong,Jiang, Ira W,Deveson, Gianina,Ravenscroft, Schahram,Akbarian, Michael A,Eberle, Kym M,Boycott, Tomi,Pastinen, Bernard,Brais, Stephan,Zuchner, Matt C,Danzi

Nature genetics · 2024-06-27

pmid:38937606

Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population.

Toshiyuki,Kakumoto, Kenta,Orimo, Takashi,Matsukawa, Jun,Mitsui, Tomohiko,Ishihara, Osamu,Onodera, Yuta,Suzuki, Shinichi,Morishita, Tatsushi,Toda, Shoji,Tsuji

European journal of human genetics : EJHG · 2024-11-27

pmid:39604554

Deep Intronic

David,Pellerin, Matt C,Danzi, Carlo,Wilke, Mathilde,Renaud, Sarah,Fazal, Marie-Josée,Dicaire, Carolin K,Scriba, Catherine,Ashton, Christopher,Yanick, Danique,Beijer, Adriana,Rebelo, Clarissa,Rocca, Zane,Jaunmuktane, Joshua A,Sonnen, Roxanne,Larivière, David,Genís, Laura,Molina Porcel, Karine,Choquet, Rawan,Sakalla, Sylvie,Provost, Rebecca,Robertson, Xavier,Allard-Chamard, Martine,Tétreault, Sarah J,Reiling, Sara,Nagy, Vikas,Nishadham, Meera,Purushottam, Seena,Vengalil, Mainak,Bardhan, Atchayaram,Nalini, Zhongbo,Chen, Jean,Mathieu, Rami,Massie, Colin H,Chalk, Anne-Louise,Lafontaine, François,Evoy, Marie-France,Rioux, Jiannis,Ragoussis, Kym M,Boycott, Marie-Pierre,Dubé, Antoine,Duquette, Henry,Houlden, Gianina,Ravenscroft, Nigel G,Laing, Phillipa J,Lamont, Mario A,Saporta, Rebecca,Schüle, Ludger,Schöls, Roberta,La Piana, Matthis,Synofzik, Stephan,Zuchner, Bernard,Brais

The New England journal of medicine · 2022-12-14

pmid:36516086

An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.

Haloom,Rafehi, Justin,Read, David J,Szmulewicz, Kayli C,Davies, Penny,Snell, Liam G,Fearnley, Liam,Scott, Mirja,Thomsen, Greta,Gillies, Kate,Pope, Mark F,Bennett, Jacob E,Munro, Kathie J,Ngo, Luke,Chen, Mathew J,Wallis, Ernest G,Butler, Kishore R,Kumar, Kathy Hc,Wu, Susan E,Tomlinson, Stephen,Tisch, Abhishek,Malhotra, Matthew,Lee-Archer, Egor,Dolzhenko, Michael A,Eberle, Leslie J,Roberts, Brent L,Fogel, Norbert,Brüggemann, Katja,Lohmann, Martin B,Delatycki, Melanie,Bahlo, Paul J,Lockhart

American journal of human genetics · 2022-12-08

pmid:36493768

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)

Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.

Julia A,Hisey, Chiara,Masnovo, Sergei M,Mirkin

NAR molecular medicine · 2024-12-05

pmid:39723156

No evidence for association between GAA-FGF14 expansion and early onset cerebellar ataxia: a study on 85 undiagnosed patients.

Clarisse,Delvallee, Nadège,Calmels, Thomas,Bogdan, Christine,Tranchant, Mathieu,Anheim, Thomas,Wirth

Journal of neurology · 2024-12-12

pmid:39666057

How to distinguish spinocerebellar ataxia 27B from late onset cerebellar ataxia: insights from a case-control study.

Raquel,Pinheiro-Barbosa, Cheick,Cissé, Paulo,Bastos, Clémence,Leung, Anne Pavy-le,Traon, Marc,Kermorgant, Fabrice,Bonneville, Mathilde,Renaud, Cecile,Bonnet, Marion,Wandzel, Virginie,Roth, Olivier,Rascol, Fabienne,Ory-Magne, Margherita,Fabbri

Journal of neurology · 2024-12-12

pmid:39666053

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

Spinocerebellar Ataxia Type 27B (SCA27B): A Hereditary Ataxia in Portugal.

Vítor,Mendes Ferreira, Marta,Magriço, Bruna,Meira, Raquel,Barbosa

Acta medica portuguesa · 2024-10-11

pmid:39392764

Somatic instability of the FGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum.

David,Pellerin, Jean-Loup,Méreaux, Susana,Boluda, Matt C,Danzi, Marie-Josée,Dicaire, Claire-Sophie,Davoine, David,Genis, Guinevere,Spurdens, Catherine,Ashton, Jillian M,Hammond, Brandon J,Gerhart, Viorica,Chelban, Phuong U,Le, Maryam,Safisamghabadi, Christopher,Yanick, Hamin,Lee, Sathiji K,Nageshwaran, Gabriel,Matos-Rodrigues, Zane,Jaunmuktane, Kevin,Petrecca, Schahram,Akbarian, André,Nussenzweig, Karen,Usdin, Mathilde,Renaud, Céline,Bonnet, Gianina,Ravenscroft, Mario A,Saporta, Jill S,Napierala, Henry,Houlden, Ira W,Deveson, Marek,Napierala, Alexis,Brice, Laura,Molina Porcel, Danielle,Seilhean, Stephan,Zuchner, Alexandra,Durr, Bernard,Brais

Brain : a journal of neurology · 2024-10-08

pmid:39378335

Genetic profiles of multiple system atrophy revealed by exome sequencing, long-read sequencing and spinocerebellar ataxia repeat expansion analysis.

Xu-Ying,Li, Hong,Lai, Xian,Li, Fanxi,Xu, Yang,Song, Zhanjun,Wang, Qibin,Li, Ruichai,Lin, Zhiheng,Xu, Chaodong,Wang

European journal of neurology · 2024-08-17

pmid:39152783

Somatic instability of the

medRxiv : the preprint server for health sciences · 2024-07-03

pmid:39006414