Identification and characterisation of a large Senataxin (SETX) gene duplication in ataxia with ocular apraxia type 2 (AOA2)

被引：15

作者：

Arning, Larissa ^{[1
]}

Schoels, Ludger ^{[2
]}

Cin, Huriye ^{[1
]}

Souquet, Manfred ^{[3
]}

Epplen, Joerg T. ^{[1
]}

Timmann, Dagmar ^{[4
]}

机构：

[1] Ruhr Univ Bochum, Dept Human Genet, D-44780 Bochum, Germany

[2] Univ Tubingen, Dept Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

[3] Beckman Coulter, GenomeLab, Krefeld, Germany

[4] Univ Duisburg Essen, Dept Neurol, Essen, Germany

来源：

NEUROGENETICS | 2008年 / 9卷 / 04期

关键词：

AOA2; Senataxin; duplication; ataxia;

D O I：

10.1007/s10048-008-0139-z

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 alpha-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.

引用

页码：295 / 299

页数：5

共 12 条

[1] DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4) [J].

Chen, YZ ;

Bennett, CL ;

Huynh, HM ;

Blair, IP ;

Puls, I ;

Irobi, J ;

Dierick, I ;

Abel, A ;

Kennerson, ML ;

Rabin, BA ;

Nicholson, GA ;

Auer-Grumbach, M ;

Wagner, K ;

De Jonghe, P ;

Griffin, JW ;

Fischbeck, KH ;

Timmerman, V ;

Cornblath, DR ;

Chance, PF .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (06) :1128-1135

[2] Ataxia with oculomotor apraxia type 2 -: A clinical, pathologic, and genetic study [J].

Criscuolo, C ;

Chessa, L ;

Di Giandomenico, S ;

Mancini, P ;

Saccá, F ;

Grieco, GS ;

Piane, M ;

Barbieri, F ;

De Michele, G ;

Banfi, S ;

Pierelli, F ;

Rizzuto, N ;

Santorelli, FM ;

Gallosti, L ;

Filla, A ;

Casali, C .

NEUROLOGY, 2006, 66 (08) :1207-1210

[3] MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder [J].

Delia, D ;

Piane, M ;

Buscemi, G ;

Savio, C ;

Palmeri, S ;

Lulli, P ;

Carlessi, L ;

Fontanella, E ;

Chessa, L .

HUMAN MOLECULAR GENETICS, 2004, 13 (18) :2155-2163

[4] Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder [J].

Fernet, M ;

Gribaa, M ;

Salih, MAM ;

Seidahmed, MZ ;

Hall, J ;

Koenig, M .

HUMAN MOLECULAR GENETICS, 2005, 14 (02) :307-318

[5] Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2 [J].

Fogel, Brent L. ;

Perlman, Susan .

NEUROLOGY, 2006, 67 (11) :2083-2084

[6] Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2:: a clinical and genetic study in 18 patients [J].

Le Ber, I ;

Bouslam, N ;

Rivaud-Péchoux, S ;

Guimaraes, J ;

Benomar, A ;

Chamayou, C ;

Goizet, C ;

Moreira, MC ;

Klur, S ;

Yahyaoui, M ;

Agid, Y ;

Koenig, M ;

Stevanin, G ;

Brice, A ;

Dürr, A .

BRAIN, 2004, 127 :759-767

[7] Cerebellar ataxia with oculomotor apraxia type 1:: clinical and genetic studies [J].

Le Ber, I ;

Moreira, MC ;

Rivaud-Péchoux, S ;

Chamayou, C ;

Ochsner, F ;

Kuntzer, T ;

Tardieu, M ;

Saïd, G ;

Habert, MO ;

Demarquay, G ;

Tannier, C ;

Beis, JM ;

Brice, A ;

Koenig, M ;

Dürr, A .

BRAIN, 2003, 126 :2761-2772

[8] Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2 [J].

Moreira, MC ;

Klur, S ;

Watanabe, M ;

Németh, AH ;

Le Ber, I ;

Moniz, JC ;

Tranchant, C ;

Aubourg, P ;

Tazir, M ;

Schöls, L ;

Pandolfo, M ;

Schulz, JB ;

Pouget, J ;

Calvas, P ;

Shizuka-Ikeda, M ;

Shoji, M ;

Tanaka, M ;

Izatt, L ;

Shaw, CE ;

M'Zahem, A ;

Dunne, E ;

Bomont, P ;

Benhassine, T ;

Bouslam, N ;

Stevanin, G ;

Brice, A ;

Guimaraes, J ;

Mendonça, P ;

Barbot, C ;

Coutinho, P ;

Sequeiros, J ;

Dürr, A ;

Warter, JM ;

Koenig, M .

NATURE GENETICS, 2004, 36 (03) :225-227

[9] Spinocerebellar ataxia with ocular motor apraxia and DNA repair [J].

Onodera, Osamu .

NEUROPATHOLOGY, 2006, 26 (04) :361-367

[10] Analysis of newly identified low copy AluYj subfamily [J].

Park, ES ;

Huh, JW ;

Kim, TH ;

Kwak, KD ;

Kim, W ;

Kim, HS .

GENES & GENETIC SYSTEMS, 2005, 80 (06) :415-422

← 1 2 →