Ignatius, E; Isohanni, P; Pohjanpelto, M; Lahermo, P; Ojanen, S; Brilhante, V; Palin, E; Suomalainen, A; Lönnqvist, T; Carroll, CJ
(2020)
Genetic background of ataxia in children younger than 5 years in Finland.
Neurol Genet, 6 (4).
e444.
ISSN 2376-7839
https://doi.org/10.1212/NXG.0000000000000444
SGUL Authors: Carroll, Christopher John
Abstract
Objective: To characterize the genetic background of molecularly undefined childhood-onset ataxias in Finland. Methods: This study examined a cohort of patients from 50 families with onset of an ataxia syndrome before the age of 5 years collected from a single tertiary center, drawing on the advantages offered by next generation sequencing. A genome-wide genotyping array (Illumina Infinium Global Screening Array MD-24 v.2.0) was used to search for copy number variation undetectable by exome sequencing. Results: Exome sequencing led to a molecular diagnosis for 20 probands (40%). In the 23 patients examined with a genome-wide genotyping array, 2 additional diagnoses were made. A considerable proportion of probands with a molecular diagnosis had de novo pathogenic variants (45%). In addition, the study identified a de novo variant in a gene not previously linked to ataxia: MED23. Patients in the cohort had medically actionable findings. Conclusions: There is a high heterogeneity of causative mutations in this cohort despite the defined age at onset, phenotypical overlap between patients, the founder effect, and genetic isolation in the Finnish population. The findings reflect the heterogeneous genetic background of ataxia seen worldwide and the substantial contribution of de novo variants underlying childhood ataxia.
Item Type: |
Article
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Additional Information: |
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Neurol Genet |
ISSN: |
2376-7839 |
Language: |
eng |
Dates: |
Date | Event |
---|
August 2020 | Published | 5 June 2020 | Published Online | 27 April 2020 | Accepted |
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Publisher License: |
Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 |
PubMed ID: |
32637629 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112150 |
Publisher's version: |
https://doi.org/10.1212/NXG.0000000000000444 |
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