Movement disorders : official journal of the Movement Disorder Society · 2025
Identification of GGC Repeat Expansions in ZFHX3 among Chilean Movement Disorder Patients.
СтатьяНазвание и аннотация: Перевод в очереди
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Saffie-Awad Paula, Moller Abraham, Daida Kensuke, Alvarez Jerez Pilar, Chen Zhongbo, Anderson Zachary B, Isayan Mariam, Paquette Kimberly, Gibson Sophia B, Fulcher Madison, Miano-Burkhardt Abigail, Malik Laksh, Baker Breeana, Jarreau Paige, Houlden Henry, Ryten Mina, Gu Bida, Chaisson Mark J P, Miller Danny E, Chaná-Cuevas Pedro, Blauwendraat Cornelis, Singleton Andrew B, Billingsley Kimberley J
Аннотация
BACKGROUND: Hereditary ataxias are genetically diverse, yet up to 75% remain undiagnosed due to technological and financial barriers. The GGC repeat expansion in ZFHX3, responsible for spinocerebellar ataxia type 4 (SCA4), has only been described in individuals of Northern Europeandescent.
OBJECTIVE: Uncover the genetic etiology of suspected hereditary movement disorders.
METHODS: We performed Oxford Nanopore long-read genome sequencing on 15 individuals with suspected hereditary movement disorders. Using variant calling and ancestry inference tools.
RESULTS: We identified ZFHX3 GGC expansions (47-55 repeats) in 4 patients with progressive ataxia, polyneuropathy, and vermis atrophy. One presented with rapidly progressive parkinsonism-ataxia, expanding the known phenotype. Longer expansions correlated with earlier onset and severity. All carriers shared single nucleotide variants (SNVs) associated with the Swedish founder haplotype, and methylation analysis confirmed allele-specific hypermethylation.
CONCLUSION: These represent the first SCA4 cases identified outside Northern Europe. Our findings highlight the value of long-read sequencing in resolving undiagnosed movement disorders. Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
OBJECTIVE: Uncover the genetic etiology of suspected hereditary movement disorders.
METHODS: We performed Oxford Nanopore long-read genome sequencing on 15 individuals with suspected hereditary movement disorders. Using variant calling and ancestry inference tools.
RESULTS: We identified ZFHX3 GGC expansions (47-55 repeats) in 4 patients with progressive ataxia, polyneuropathy, and vermis atrophy. One presented with rapidly progressive parkinsonism-ataxia, expanding the known phenotype. Longer expansions correlated with earlier onset and severity. All carriers shared single nucleotide variants (SNVs) associated with the Swedish founder haplotype, and methylation analysis confirmed allele-specific hypermethylation.
CONCLUSION: These represent the first SCA4 cases identified outside Northern Europe. Our findings highlight the value of long-read sequencing in resolving undiagnosed movement disorders. Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.