SCA4: Correlation of age of onset and ZFHX3 repeat length
Wallenius, Joel LU
and Puschmann, Andreas
LU
(2024)
In Parkinsonism and Related Disorders
122.
p.29-30
- Abstract
- Background: Four reports, published in the form of pre-prints or peer-reviewed articles, have recently described that spinocerebellar ataxia type 4 (SCA4) is caused by expansion of GGC repeats in exon 10 of ZFHX3 . None of the independent reports have definitely established if longer repeats are associated with earlier disease onset.
Methods: We compiled clinical and genetic data from all four published reports.
Results: Long-read sequencing data was publicly available from three reports, while short-read data was available from two. Age of onset data was available from three reports. Repeat length determined through short-read sequencing correlated inversely with age at disease onset in patients who have up to 50 GGC... (More) - Background: Four reports, published in the form of pre-prints or peer-reviewed articles, have recently described that spinocerebellar ataxia type 4 (SCA4) is caused by expansion of GGC repeats in exon 10 of ZFHX3 . None of the independent reports have definitely established if longer repeats are associated with earlier disease onset.
Methods: We compiled clinical and genetic data from all four published reports.
Results: Long-read sequencing data was publicly available from three reports, while short-read data was available from two. Age of onset data was available from three reports. Repeat length determined through short-read sequencing correlated inversely with age at disease onset in patients who have up to 50 GGC trinucleotide repeats (150 base pairs). Long-read sequencing showed clear inverse correlation of age at onset also for longer repats, but results from only six SCA4 patients are so far (27 Jan 2024) available publicly. Methods to determine repeat lengths differed partly between the studies.
Conclusions: In SCA4, longer GCC repeats in ZFHX3 appear to be associated with earlier disease onset. In expanded alleles, the GGC repeat is close to or longer than the typical short-read read length of 150 bp. Determining exact read lengths by short-read sequencing may be prone to errors in longer repeats, but long-read technology is still not widely available and is more expensive. Publication of results from additional patients will make it possible to examine this association further. We expect such data will be available at the time of the IAPRD 2024 World Congress, where we will present updated information (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7a895363-67aa-4115-b011-d1beea1578db
- author
- Wallenius, Joel
LU
and Puschmann, Andreas
LU
- organization
- publishing date
- 2024-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Parkinsonism and Related Disorders
- volume
- 122
- article number
- 106644
- pages
- 29 - 30
- publisher
- Elsevier
- ISSN
- 1873-5126
- DOI
- 10.1016/j.parkreldis.2024.106644
- language
- English
- LU publication?
- yes
- id
- 7a895363-67aa-4115-b011-d1beea1578db
- date added to LUP
- 2024-10-01 15:57:43
- date last changed
- 2024-10-02 13:49:43
@misc{7a895363-67aa-4115-b011-d1beea1578db,
abstract = {{Background: Four reports, published in the form of pre-prints or peer-reviewed articles, have recently described that spinocerebellar ataxia type 4 (SCA4) is caused by expansion of GGC repeats in exon 10 of ZFHX3 . None of the independent reports have definitely established if longer repeats are associated with earlier disease onset.<br/><br/>Methods: We compiled clinical and genetic data from all four published reports.<br/><br/>Results: Long-read sequencing data was publicly available from three reports, while short-read data was available from two. Age of onset data was available from three reports. Repeat length determined through short-read sequencing correlated inversely with age at disease onset in patients who have up to 50 GGC trinucleotide repeats (150 base pairs). Long-read sequencing showed clear inverse correlation of age at onset also for longer repats, but results from only six SCA4 patients are so far (27 Jan 2024) available publicly. Methods to determine repeat lengths differed partly between the studies.<br/><br/>Conclusions: In SCA4, longer GCC repeats in ZFHX3 appear to be associated with earlier disease onset. In expanded alleles, the GGC repeat is close to or longer than the typical short-read read length of 150 bp. Determining exact read lengths by short-read sequencing may be prone to errors in longer repeats, but long-read technology is still not widely available and is more expensive. Publication of results from additional patients will make it possible to examine this association further. We expect such data will be available at the time of the IAPRD 2024 World Congress, where we will present updated information}},
author = {{Wallenius, Joel and Puschmann, Andreas}},
issn = {{1873-5126}},
language = {{eng}},
month = {{05}},
note = {{Conference Abstract}},
pages = {{29--30}},
publisher = {{Elsevier}},
series = {{Parkinsonism and Related Disorders}},
title = {{SCA4: Correlation of age of onset and ZFHX3 repeat length}},
url = {{http://dx.doi.org/10.1016/j.parkreldis.2024.106644}},
doi = {{10.1016/j.parkreldis.2024.106644}},
volume = {{122}},
year = {{2024}},
}