@article{45b88b62299a464e95898e224d881b65,
title = "The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin",
abstract = "The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxiatelangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3′phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.",
author = "Moreira, {Maria C{\'e}u} and Clara Barbot and Nobutada Tachi and Naoki Kozuka and Eiji Uchida and Toby Gibson and Pedro Mendon{\c c}a and Manuela Costa and Jos{\'e} Barros and Takayuki Yanagisawa and Mitsunori Watanabe and Yoshio Ikeda and Masashi Aoki and Tetsuya Nagata and Paula Coutinho and Jorge Sequeiros and Michel Koenig",
note = "Funding Information: We wish to express our gratitude to all patients and families for their collaboration, as well as to R. Chor{\~a}o, C. Ferreira, I. Fineza, K. Dias, J.P. Monteiro, K. Sasaki, M. Shizuka-Ikeda, C. Alves, L. Pereira and A. Amorim. We are indebted to J.-L. Mandel for his enthusiastic support and fruitful discussions; to D. Simon, H. Puccio and A. Buj-Bello for their support and their sharing of biological material; and to D. Sommer-Stephan, S. Vicaire, E. Troesch, F. Ruffenach, I. Colas and T. Matam{\'a} for excellent technical help. Family characterization and DNA sampling were supported by a grant from the Comiss{\~a}o de Fomento da Investiga{\c c}{\~a}o em Cuidados de Sa{\'u}de, Portuguese Ministry of Health (no. 207/99) and grants from Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (Portuguese Ministry of Science and Technology) and from the Portuguese Ministry of Health (projects PRAXIS/PSAU/P/SAU/84/96, POCTI 34535/99, POCTI 32643/99 and PECS/C/SAU/219/95). Genetic studies were supported by funds from the Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, the Centre National de la Recherche Scientifique, the H{\^o}pitaux Universitaires de Strasbourg, and the Human Frontier Science Program (to M.K. and T.B.). M.C.M. has graduate fellowship PRAXIS XXI/BD/18169/98 from the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia— Portugal.",
year = "2001",
doi = "10.1038/ng1001-189",
language = "English",
volume = "29",
pages = "189--193",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",
}