ArticleAmerican journal of human genetics2024
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.
Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Epidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2025Pooled it
- Characterising the motif composition and allele length distribution of ZFHX3 GGC repeat expansions in amyotrophic lateral sclerosis.Journal of human genetics · 2026Article
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- Frequency of ZFHX3-Mediated Spinocerebellar Ataxia 4 in a US Undiagnosed Ataxia Cohort.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Dissecting the relationship between haplotypes around ATXN2 CAG repeats and the number of CAA interruptions by long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing.Brain : a journal of neurology · 2026Article
- GGC repeat expansions within new open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy.Nature genetics · 2026Article
- Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.Frontiers in immunology · 2026Article
- Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS.Cell reports. Medicine · 2025Article
- Genetic background of neurological disorders with basal ganglia calcification.Journal of neurology · 2025Article
- Barriers to clinical genetic testing in movement disorders.Current opinion in neurology · 2025Review
- Identification of GGC Repeat Expansions in ZFHX3 among Chilean Movement Disorder Patients.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Exploration of Neurodegenerative Diseases Using Long-Read Sequencing and Optical Genome Mapping Technologies.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Repeat expansion disorders.Practical neurology · 2025Review
- Recent progress in oculopharyngodistal myopathy research from clinical and genetic viewpoints.Journal of neuromuscular diseases · 2025Review
- Targeted Long-Read Sequencing as a Single Assay Improves the Diagnosis of Spastic-Ataxia Disorders.Annals of clinical and translational neurology · 2025Article
- STRchive: a dynamic resource detailing population-level and locus-specific insights at tandem repeat disease loci.Genome medicine · 2025Article
- Article
- ONT in Clinical Diagnostics of Repeat Expansion Disorders: Detection and Reporting Challenges.International journal of molecular sciences · 2025Article
- The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.Movement disorders : official journal of the Movement Disorder Society · 2025Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal-dominant ataxia with sensory and autonomic neuropathy is a highly specific combined phenotype that we described in two Swedish kindreds in 2014; its genetic cause had remained unknown. Here, we report the discovery of exonic GGC trinucleotide repeat expansions, encoding poly-glycine, in zinc finger homeobox 3 (ZFHX3) in these families. The expansions were identified in whole-genome datasets within genomic segments that all affected family members shared. Non-expanded alleles carried one or more interruptions within the repeat. We also found ZFHX3 repeat expansions in three additional families, all from the region of Skåne in southern Sweden. Individuals with expanded repeats developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. Anticipation was observed in all families and correlated with different repeat lengths determined through long-read sequencing in two family members. The most severely affected individuals had marked autonomic dysfunction, with severe orthostatism as the most disabling clinical feature. Neuropathology revealed p62-positive intracytoplasmic and intranuclear inclusions in neurons of the central and enteric nervous system, as well as alpha-synuclein positivity. ZFHX3 is located within the 16q22 locus, to which spinocerebellar ataxia type 4 (SCA4) repeatedly had been mapped; the clinical phenotype in our families corresponded well with the unique phenotype described in SCA4, and the original SCA4 kindred originated from Sweden. ZFHX3 has known functions in neuronal development and differentiation n both the central and peripheral nervous system. Our findings demonstrate that SCA4 is caused by repeat expansions in ZFHX3.
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