title: Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.
abstract: Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Date
authors.forename: O
authors.initials: O
authors.lastname: Onodera
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: K
authors.initials: K
authors.lastname: Uekawa
authors.forename: S
authors.initials: S
authors.lastname: Igarashi
authors.forename: R
authors.initials: R
authors.lastname: Koike
authors.forename: T
authors.initials: T
authors.lastname: Hiroi
authors.forename: T
authors.initials: T
authors.lastname: Yuasa
authors.forename: Y
authors.initials: Y
authors.lastname: Awaya
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Nagatomo
authors.forename: Y
authors.initials: Y
authors.lastname: Sekijima
authors.forename: I
authors.initials: I
authors.lastname: Kawachi
authors.forename: Y
authors.initials: Y
authors.lastname: Takiyama
authors.forename: M
authors.initials: M
authors.lastname: Nishizawa
authors.forename: N
authors.initials: N
authors.lastname: Fukuhara
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Sugano
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001072:Apraxias / Q000150:complications / Q000235:genetics*; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D009801:Oculomotor Muscles / Q000503:physiopathology*; D010375:Pedigree; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: C438188:APTX protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012709:Serum Albumin