Genetic background of ataxia in children younger than 5 years in Finland

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http://hdl.handle.net/10138/322106

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Ignatius , E , Isohanni , P , Pohjanpelto , M , Lahermo , P , Ojanen , S , Brilhante , V , Palin , E , Suomalainen , A , Lönnqvist , T & Carroll , C J 2020 , ' Genetic background of ataxia in children younger than 5 years in Finland ' , Neurology Genetics , vol. 6 , no. 4 , 444 . https://doi.org/10.1212/NXG.0000000000000444

Title: Genetic background of ataxia in children younger than 5 years in Finland
Author: Ignatius, Erika; Isohanni, Pirjo; Pohjanpelto, Max; Lahermo, Päivi; Ojanen, Simo; Brilhante, Virginia; Palin, Eino; Suomalainen, Anu; Lönnqvist, Tuula; Carroll, Christopher J.
Contributor: University of Helsinki, HUS Children and Adolescents
University of Helsinki, HUS Children and Adolescents
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Veterinary Biosciences
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Anu Wartiovaara / Principal Investigator
University of Helsinki, HUS Helsinki and Uusimaa Hospital District
University of Helsinki, HUS Children and Adolescents
Date: 2020-08
Language: eng
Number of pages: 9
Belongs to series: Neurology Genetics
ISSN: 2376-7839
URI: http://hdl.handle.net/10138/322106
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.
Subject: SPINOCEREBELLAR-ATAXIA
CEREBELLAR-ATAXIA
ONSET
MUTATIONS
PROTEIN
ASSOCIATION
ATROPHY
DELAY
MODEL
TOOL
1184 Genetics, developmental biology, physiology
3112 Neurosciences
3123 Gynaecology and paediatrics
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