title: A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia.
abstract: Spinocerebellar ataxia type 11 (SCA11) is rare and has previously been described in four families worldwide. We report a Danish family with onset of symptoms in early childhood and affected family members in two generations. The proband, a Danish female born in 1968, and family members were examined. Exome sequencing was performed and a "movement disorders" gene panel consisting of approximately 200 genes was used for filtering, while Sanger sequencing was used for subsequent testing for the mutation in the family. Onset of symptoms in affected family members was in early childhood. A novel frameshift mutation (c.1205_1207delinsA) in the tau-tubulin kinase 2 encoding gene, TTBK2, was identified, which was compatible with a diagnosis of SCA11. The mutation was subsequently identified in her two affected sons but not in the unaffected parents or her unaffected brother. This report further delineates the phenotypic spectrum of the rare SCA11 disease. In contrast to previously reported cases, onset of symptoms was in early childhood and the mutation was de novo in the proband.
authors.affiliation: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. suzanne.lindquist@regionh.dk.|Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. suzanne.lindquist@regionh.dk.
authors.forename: Suzanne Granhøj
authors.initials: SG
authors.lastname: Lindquist
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Lisbeth Birk
authors.initials: LB
authors.lastname: Møller
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Christine I
authors.initials: CI
authors.lastname: Dali
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Marner
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Kamsteeg
authors.affiliation: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Jørgen Erik
authors.initials: JE
authors.lastname: Nielsen
authors.affiliation: Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Lena Elisabeth
authors.initials: LE
authors.lastname: Hjermind
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D004252:DNA Mutational Analysis; D003718:Denmark; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases
keywords: Cerebellum; Genetics; Neurodegeneration; Spinocerebellar ataxia