title: Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation.
abstract: Autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders primarily affecting the cerebellum. Genetically, 26 different loci have been identified so far, although the corresponding gene has not yet been determined for 10 of them. Recently, mutations in the ATPase family gene 3-like 2 gene were presented to cause SCA type 28. To define the frequency of SCA28 mutations, we performed molecular genetic analyses in 140 unrelated familial cases with ataxia. Among other variations, we found a novel missense mutation at an evolutionarily conserved amino-acid position using a single-strand conformation polymorphism approach, followed by DNA sequencing. This amino-acid exchange p.E700K was detected in a four-generation German family and was not observed in a survey of 400 chromosomes from healthy control individuals.
authors.affiliation: Institute for Human Genetics, University of Luebeck, Ratzeburger Allee 160, Luebeck, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Edener
authors.forename: Janine
authors.initials: J
authors.lastname: Wöllner
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.forename: Zacharias
authors.initials: Z
authors.lastname: Kohl
authors.forename: Stefan
authors.initials: S
authors.lastname: Schilling
authors.forename: Friedmar
authors.initials: F
authors.lastname: Kreuz
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
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: D049069:ATP-Dependent Proteases / Q000235:genetics* / Q000378:metabolism*; D000074183:ATPases Associated with Diverse Cellular Activities; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D049069:ATP-Dependent Proteases; C120699:AFG3L2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities