Abstract
Autosomal recessive cerebellar ataxia (ARCA) is a group of neurological disorders characterized by degeneration or abnormal development of the cerebellum and spinal cord. ARCA is clinically and genetically highly heterogeneous, with over 20 genes involved. Exome sequencing of a girl with ARCA from non-consanguineous Dutch parents revealed two pathogenic variants c.37G>C; p.D13H and c.946A>T; p.K316* in CWF19L1, a gene with an unknown function, recently reported to cause ARCA in a Turkish family. Sanger sequencing showed that the c.37G>C variant was inherited from the father and the c.946A>T variant from the mother. Pathogenicity was based on the damaging effect on protein function as the c.37G>C variant changed the highly conserved, negatively charged aspartic acid to the positively charged histidine and the c.946A>T variant introduced a premature stop codon. In addition, 27 patients with ARCA were tested for pathogenic variants in CWF19L1, however, no pathogenic variants were identified. Our data confirm CWF19L1 as a novel but rare gene causing ARCA.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Anheim M, Tranchant C, Koenig M : The autosomal recessive cerebellar ataxias. N Engl J Med 2012; 366: 636–646.
Sailer A, Houlden H : Recent advances in the genetics of cerebellar ataxias. Curr Neurol Neurosci Rep 2012; 12: 227–236.
Burns R, Majczenko K, Xu J et al: Homozygous splice mutation in CWF19L1 in a Turkish family with recessive ataxia syndrome. Neurology 2014; 83: 2175–2182.
Li H, Durbin R : Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25: 1754–1760.
Li H, Durbin R : Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010; 26: 589–595.
McKenna A, Hanna M, Banks E et al: The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010; 20: 1297–1303.
DePristo MA, Banks E, Poplin R et al: A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 2011; 43: 491–498.
Liu X, Jian X, Boerwinkle E : dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat 2013; 34: E2393–E2402.
Nishioka M, Kohno T, Tani M : MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer. Proc Natl Acad Sci USA 2002; 99: 12269–12274.
Alazami AM, Kentab AY, Fageih E et al: A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B. J Med Genet 2015; 52: 400–404.
Acknowledgements
This work is supported by the Alma in Silico project, which is financed by the Interreg IV European funds, The Walloon Region, The North Rhine Westphalia, The Flemish Community, The Belgian Province of Limburg and The Dutch Province of Limburg, as well as by the Universities of Maastricht and Liège, by the Prinses Beatrix Spierfonds (grant W.OR11-24) and the Stichting Metakids.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Nguyen, M., Boesten, I., Hellebrekers, D. et al. Pathogenic CWF19L1 variants as a novel cause of autosomal recessive cerebellar ataxia and atrophy. Eur J Hum Genet 24, 619–622 (2016). https://doi.org/10.1038/ejhg.2015.158
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ejhg.2015.158
This article is cited by
-
RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators
Nature Biotechnology (2024)
-
Novel CWF19L1 mutations in patients with spinocerebellar ataxia, autosomal recessive 17
Journal of Human Genetics (2023)
-
Pathogenic SLIRP variants as a novel cause of autosomal recessive mitochondrial encephalomyopathy with complex I and IV deficiency
European Journal of Human Genetics (2021)
-
Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability
Human Genetics (2018)
-
Systematic review of autosomal recessive ataxias and proposal for a classification
Cerebellum & Ataxias (2017)
