title: Pathogenic CWF19L1 variants as a novel cause of autosomal recessive cerebellar ataxia and atrophy.
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.
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.|Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Boesten
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Debby M E I
authors.initials: DM
authors.lastname: Hellebrekers
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Jo
authors.initials: J
authors.lastname: Vanoevelen
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Kamps
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Koning
authors.affiliation: Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Irenaeus F M
authors.initials: IF
authors.lastname: de Coo
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.|Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.|Maastricht Center of Systems Biology (MaCSBio), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Mike
authors.initials: M
authors.lastname: Gerards
authors.affiliation: Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, Maastricht, The Netherlands.|Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Hubert J M
authors.initials: HJ
authors.lastname: Smeets
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D018388:Codon, Terminator; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C000595891:CWF19L1 protein, human; D018797:Cell Cycle Proteins; D018388:Codon, Terminator