Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene

• Published in: Nature genetics Vol. 29; no. 2; pp. 184 - 188
• Main Authors: Takiyama, Yoshihisa, Sakai, Tetsuo, Igarashi, Shuichi, Nishizawa, Masatoyo, Awaya, Yutaka, Uekawa, Kazutoshi, Saito, Kayoko, Takahashi, Tatsuya, Date, Hidetoshi, Kawachi, Izumi, Sugano, Sumio, Iwabuchi, Kiyoshi, Koike, Ryoko, Fukuhara, Nobuyoshi, Tanaka, Hajime, Hiroi, Tadashi, Sekijima, Yoshiki, Tsuji, Shoji, Onodera, Osamu, Yuasa, Tatsuhiko, Nagatomo, Hideki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-10-2001
• Subjects: Amino Acid Sequence; Amino acids; Animals; aprataxin; Apraxia; Apraxias - complications; Apraxias - genetics; APTX gene; Ataxia; Ataxia - complications; Ataxia - genetics; Biological and medical sciences; chromosome 9; Chromosome Mapping; Chromosomes, Human, Pair 9; Complications and side effects; Diagnosis; Disease; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; Female; Friedreich's ataxia; Fundamental and applied biological sciences. Psychology; Gene mutations; Genes. Genome; Genetic aspects; Genetic Linkage; Genotype & phenotype; Haplotypes; Hospitals; Humans; Identification and classification; Male; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; Neurology; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Oculomotor Muscles - physiopathology; oculomotor system; Pediatrics; Pedigree; Phylogeny; Protein metabolism disorders; Psychiatry; Publishing; Risk factors; Sequence Homology, Amino Acid; Serum Albumin - metabolism; Japan; Nervous system diseases; Albumin; Cerebral disorder; Hypoalbuminemia; Metabolic disorder; Gene; Central nervous system disease; Ataxia; Early; Apraxia; Earliness; Mutation; Neurological disorder
• DOI: 10.1038/ng1001-184
• EISSN: 1546-1718
• ISSN: 1061-4036

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.