Abstract
Autosomal recessive cerebellar ataxia with ocular apraxia type 2 (AOA2) is a neurodegenerative disorder characterised by early onset cerebellar ataxia, sensory-motor neuropathy and frequently increased levels of α-fetoprotein. We describe a male patient with a phenotype highly suggestive of AOA2, but only one point mutation found by sequencing of the SETX gene. Further analysis revealed a large out-of-frame tandem duplication, encompassing exons 7, 8, 9 and 10. This duplication event occurred obviously by unequal homologous recombination between AluY sequences. Gross SETX deletions or duplications might be an underestimated cause of AOA2.
This is a preview of subscription content, log in via an institution to check access.
References
Moreira MC, Klur S, Watanabe M, Nemeth AH, Le Ber I, Moniz JC et al (2004) Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 36:225–227 doi:10.1038/ng1303
Le Ber I, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A, Chamayou C et al (2004) Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain 127:759–767 doi:10.1093/brain/awh080
Delia D, Piane M, Buscemi G, Savio C, Palmeri S, Lulli P et al (2004) MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia telangiectasia-like disorder. Hum Mol Genet 13:2155–2163 doi:10.1093/hmg/ddh221
Fernet M, Gribaa M, Salih MA, Seidahmed MZ, Hall J, Koenig M (2005) Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder. Hum Mol Genet 14:307–318 doi:10.1093/hmg/ddi027
Le Ber I, Moreira MC, Rivaud-Pechoux S, Chamayou C, Ochsner F, Kuntzer T et al (2003) Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain 126:2761–2772 doi:10.1093/brain/awg283
Onodera O (2006) Spinocerebellar ataxia with ocular motor apraxia and DNA repair. Neuropathology 26:361–367 doi:10.1111/j.1440-1789.2006.00741.x
Woods CG, Taylor AM (1992) Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. Q J Med 82:169–179
Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J et al (2004) DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet 74:1128–1135 doi:10.1086/421054
Fogel BL, Perlman S (2006) Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. Neurology 67:2083–2084 doi:10.1212/01.wnl.0000247661.19601.28
Schöls L, Arning L, Schüle R, Epplen JT, Timmann D (2008) “Pseudodominant inheritance” of ataxia with ocular apraxia type 2 (AOA2). J Neurol 255:495–501 doi:10.1007/s00415–008–0707-z
Criscuolo C, Chessa L, Di Giandomenico S, Mancini P, Saccà F, Grieco GS et al (2006) Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study. Neurology 66:1207–1210 doi:10.1212/01.wnl.0000208402.10512.4a
Park ES, Huh JW, Kim TH, Kwak KD, Kim W, Kim HS (2005) Analysis of newly identified low copy AluYj subfamily. Genes Genet Syst 80:415 doi:10.1266/ggs.80.415
Acknowledgment
The authors would like to thank Andrea Petzold for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Arning, L., Schöls, L., Cin, H. et al. Identification and characterisation of a large Senataxin (SETX) gene duplication in ataxia with ocular apraxia type 2 (AOA2). Neurogenetics 9, 295–299 (2008). https://doi.org/10.1007/s10048-008-0139-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10048-008-0139-z