Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2

Maria-Céu Moreira (1) , Sandra Klur (1) , Mitsunori Watanabe (2) , Andrea H. Németh (3) , Isabelle Le Ber (4, 5) , José-Carlos Moniz (6) , Christine Tranchant (7) , Patrick Aubourg (8, 9) , Meriem Tazir (10) , Lüdger Schöls (11) , Massimo Pandolfo (12) , Jörg Schulz (13) , Jean Pouget (14) , Patrick Calvas (15) , Masami Shizuka-Ikeda (2) , Mikio Shoji (2) , Makoto Tanaka (2) , Louise Izatt (16) , Christopher E. Shaw (17) , Abderrahim M'Zahem , Eimear Dunne (3) , Pascale Bomont (1) , Traki Benhassine (18) , Naïma Bouslam (4, 5) , Giovanni Stevanin (4, 5) , Alexis Brice (4, 5) , João Guimarães (19) , Pedro Mendonça (20) , Clara Barbot (21, 22) , Paula Coutinho (21) , Jorge Sequeiros (21) , Alexandra Dürr (4, 5) , Jean-Marie Warter (7) , Michel Koenig (1)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 Gunma University Graduate School of Medicine [Maebashi, Japan]
3 The Wellcome Trust Centre for Human Genetics [Oxford]
4 Neurologie Expérimentale et Thérapeutique
5 CHU Pitié-Salpêtrière [AP-HP]
6 Hospital de St. António dos Capuchos
7 HUS - Les Hôpitaux Universitaires de Strasbourg
8 Pathologie métabolique et hormonale du développement
9 Hôpital Saint-Vincent de Paul
10 Le centre hospitalier universitaire (CHU) Mustapha Pacha [Alger]
11 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
12 ULB - Université libre de Bruxelles
13 University of Tübingen
14 TIMONE - Hôpital de la Timone [CHU - APHM]
15 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
16 Guy's Hospital [London]
17 King‘s College London
18 Institut Pasteur d'Algérie
19 Hospital De Egas Moniz [Lisbon]
20 Hospital do Divino Espirito Santo
21 Universidade do Porto = University of Porto
22 Centro Hospitalar do Porto – Hospital Maria Pia

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.

Domaines: Génétique

Maria-Céu Moreira, Sandra Klur, Mitsunori Watanabe, Andrea H. Németh, Isabelle Le Ber, et al.. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nature Genetics, 2004, 36 (3), pp.225-227. ⟨10.1038/ng1303⟩. ⟨hal-04138405⟩