title: Missense exchanges in the TTBK2 gene mutated in SCA11.
abstract: The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a clinically and genetically heterogeneous group of neurological disorders with overlapping as well as highly variable phenotypes primarily affecting the cerebellum. To date, 28 different loci have been identified. Nine SCAs are caused by repeat expansions; for 14 only the chromosomal localisation is known. Recently, two frameshift mutations in the tau tubulin kinase 2 gene (TTBK2) were reported to cause SCA11. To evaluate the frequency of mutations in the TTBK2 gene, we performed molecular genetic analyses in 49 unrelated familial cases with ataxia. Sequencing all coding exons revealed, amongst others, two novel missense exchanges at evolutionarily conserved amino acid positions. Although being unique in 98 alleles of ataxia patients, a disease causing effect can be excluded with high probability for both variations. This result demonstrates the challenges in diagnostic testing for SCA11.
authors.affiliation: Institut für Humangenetik, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Edener
authors.forename: Ingo
authors.initials: I
authors.lastname: Kurth
authors.forename: Annechristin
authors.initials: A
authors.lastname: Meiner
authors.forename: Frank
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernard
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Christine
authors.initials: C
authors.lastname: Zühlke
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases