SCA4 ZFHX3

Spinocerebellar ataxia type 4 (SCA4) is a very rare progressive subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by ataxia with sensory neuropathy (adapted from Mondo)¹.

Prevalence

Observed in Swedish individuals: 2 original kindreds and 3 additional families²; common ancestral allele has been identified³.

Age of Onset Details

Typical: 37- 56; Range: 15 - 60^4,5.

Locus

hg19

chr16:72821594-72821657

hg38

chr16:72787695-72787758

t2t

chr16:78605503-78605569

Details

Disease-causing expansions range from 46 repeats⁵to 74 repeats⁴. Possible anticipation in disease^6,4; intermediate alleles may correspond to premutations⁵. Most unaffected individuals had 21 motifs, but benign alleles range from 14-26 repeats⁴.

Mechanism

GoF?

Potential RNA-mediated gain of functin mechanism theorized⁷

Year

2023⁴

Location in Gene

Last Exon (exact exon transcript dependent)

Gene Strand

Alleles

Ref. Motif

GCC

Pathogenic (ref.)

GCC

Pathogenic (gene)

CGG

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010847

omim:600223

The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.

Zhongbo,Chen, Pilar,Alvarez Jerez, Claire,Anderson, Martin,Paucar, Jasmaine,Lee, Daniel,Nilsson, Hannah,Macpherson, Annarita,Scardamaglia, Kylie,Montgomery, John,Hardy, Andrew B,Singleton, Arianna,Tucci, Katherine D,Mathews, Ying-Hui,Fu, Martin,Engvall, José,Laffita-Mesa, Inger,Nennesmo, Anna,Wedell, Louis J,Ptáček, Cornelis,Blauwendraat, Emil K,Gustavsson, Per,Svenningsson, Mina,Ryten, Henry,Houlden

Movement disorders : official journal of the Movement Disorder Society · 2024-12-05

pmid:39635987

Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.

Joel,Wallenius, Efthymia,Kafantari, Emma,Jhaveri, Sorina,Gorcenco, Adam,Ameur, Christin,Karremo, Sigurd,Dobloug, Kristina,Karrman, Tom,de Koning, Andreea,Ilinca, Maria,Landqvist Waldö, Andreas,Arvidsson, Staffan,Persson, Elisabet,Englund, Hans,Ehrencrona, Andreas,Puschmann

American journal of human genetics · 2023-11-29

pmid:38035881

Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.

Martin,Paucar, Daniel,Nilsson, Martin,Engvall, José,Laffita-Mesa, Cilla,Söderhäll, Mikael,Skorpil, Christer,Halldin, Patrik,Fazio, Kristina,Lagerstedt-Robinson, Göran,Solders, Maria,Angeria, Andrea,Varrone, Mårten,Risling, Hong,Jiao, Inger,Nennesmo, Anna,Wedell, Per,Svenningsson

Journal of internal medicine · 2024-07-07

pmid:38973251

Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.

Zhongbo,Chen, Emil K,Gustavsson, Hannah,Macpherson, Claire,Anderson, Chris,Clarkson, Clarissa,Rocca, Eleanor,Self, Pilar,Alvarez Jerez, Annarita,Scardamaglia, David,Pellerin, Kylie,Montgomery, Jasmaine,Lee, Delia,Gagliardi, Huihui,Luo, John,Hardy, James,Polke, Andrew B,Singleton, Cornelis,Blauwendraat, Katherine D,Mathews, Arianna,Tucci, Ying-Hui,Fu, Henry,Houlden, Mina,Ryten, Louis J,Ptáček

Movement disorders : official journal of the Movement Disorder Society · 2024-01-10

pmid:38197134

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

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)

Repeat length in spinocerebellar ataxia type 4 (SCA4) predicts age at onset and disease severity.

Andreas,Dalski, Martje G,Pauly, Henrike,Hanssen, Johann,Hagenah, Yorck,Hellenbroich, Christian,Schmidt, Jassemien,Strohschehn, Malte,Spielmann, Christine,Zühlke, Norbert,Brüggemann

Journal of neurology · 2024-08-02

pmid:39095619

A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.

Karla P,Figueroa, Caspar,Gross, Elena,Buena-Atienza, Sharan,Paul, Mandi,Gandelman, Naseebullah,Kakar, Marc,Sturm, Nicolas,Casadei, Jakob,Admard, Joohyun,Park, Christine,Zühlke, Yorck,Hellenbroich, Jelena,Pozojevic, Saranya,Balachandran, Kristian,Händler, Simone,Zittel, Dagmar,Timmann, Friedrich,Erdlenbruch, Laura,Herrmann, Thomas,Feindt, Martin,Zenker, Thomas,Klopstock, Claudia,Dufke, Daniel R,Scoles, Arnulf,Koeppen, Malte,Spielmann, Olaf,Riess, Stephan,Ossowski, Tobias B,Haack, Stefan M,Pulst

Nature genetics · 2024-04-29

pmid:38684900

FGF14 GAA repeat expansion and ZFHX3 GGC repeat expansion in clinically diagnosed multiple system atrophy patients.

Masaaki,Matsushima, Hiroaki,Yaguchi, Eriko,Koshimizu, Akihiko,Kudo, Shinichi,Shirai, Takeshi,Matsuoka, Shigehisa,Ura, Atsushi,Kawashima, Toshiyuki,Fukazawa, Satoko,Miyatake, Naomichi,Matsumoto, Ichiro,Yabe

Journal of neurology · 2024-03-12

pmid:38472396

Unraveling the genetic landscape of undiagnosed cerebellar ataxia in Brazilian patients.

Luiz Eduardo,Novis, Shahryar,Alavi, David,Pellerin, Marcus Vinicius,Della Coleta, Salmo,Raskin, Mariana,Spitz, Andrea,Cortese, Henry,Houlden, Helio Afonso,Teive

Parkinsonism & related disorders · 2023-12-20

pmid:38145611

The P-selectin gene polymorphism Val168Met: a novel risk marker for the occurrence of primary ventricular fibrillation during acute myocardial infarction.

Elif,Elmas, Peter,Bugert, Tatjana,Popp, Siegfried,Lang, Christel,Weiss, Michael,Behnes, Martin,Borggrefe, Thorsten,Kälsch

Journal of cardiovascular electrophysiology · 2010-11-01

pmid:20586826

Characterization of trinucleotide- and tandem repeat-containing transcripts obtained from human spinal cord cDNA library by high-density filter hybridization.

N,Kaushik, A,Malaspina, J,de Belleroche

DNA and cell biology · 2000-05-01

pmid:10855793