A polygenic heterogeneity model for common epilepsies with complex genetics

被引：44

作者：

Dibbens, L. M.

Heron, S. E.

Mulley, J. C.

机构：

[1] Womens & Childrens Hosp, Dept Med Genet, Adelaide, SA 5006, Australia

[2] Univ Adelaide, Dept Pediat, Adelaide, SA, Australia

[3] Univ Adelaide, Dept Mol & Biomed Sci, Adelaide, SA, Australia

来源：

GENES BRAIN AND BEHAVIOR | 2007年 / 6卷 / 07期

关键词：

complex genetics; epilepsy;

D O I：

10.1111/j.1601-183X.2007.00333.x

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Approximately 40% of epilepsy has a complex genetic basis with an unknown number of susceptibility genes. The effect of each susceptibility gene acting alone is insufficient to account for seizure phenotypes, but certain numbers or combinations of variations in susceptibility genes are predicted to raise the level of neuronal hyperexcitability above a seizure threshold for a given individual in a given environment. Identities of susceptibility genes are beginning to be determined, initially by translation of knowledge gained from gene discovery in the monogenic epilepsies. This entree into idiopathic epilepsies with complex genetics has led to the experimental validation of susceptibility variants in the first few susceptibility genes. The genetic architecture so far emerging from these results is consistent with what we have designated as a polygenic heterogeneity model for the epilepsies with complex genetics.

引用

页码：593 / 597

页数：5

共 52 条

[41] A KV4.2 truncation mutation in a patient with temporal lobe epilepsy [J].

Singh, Baljinder ;

Ogiwara, Ikuo ;

Kaneda, Makoto ;

Tokonami, Natsuko ;

Mazaki, Emi ;

Baba, Koichi ;

Matsuda, Kazumi ;

Inoue, Yushi ;

Yamakawa, Kazuhiro .

NEUROBIOLOGY OF DISEASE, 2006, 24 (02) :245-253

[42] A MISSENSE MUTATION IN THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR ALPHA-4 SUBUNIT IS ASSOCIATED WITH AUTOSOMAL-DOMINANT NOCTURNAL FRONTAL-LOBE EPILEPSY [J].

STEINLEIN, OK ;

MULLEY, JC ;

PROPPING, P ;

WALLACE, RH ;

PHILLIPS, HA ;

SUTHERLAND, GR ;

SCHEFFER, IE ;

BERKOVIC, SF .

NATURE GENETICS, 1995, 11 (02) :201-203

[43] A missense mutation of the Na+ channel αII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction [J].

Sugawara, T ;

Tsurubuchi, Y ;

Agarwala, KL ;

Ito, M ;

Fukuma, G ;

Mazaki-Miyazaki, E ;

Nagafuji, H ;

Noda, M ;

Imoto, K ;

Wada, K ;

Mitsudome, A ;

Kaneko, S ;

Montal, M ;

Nagata, K ;

Hirose, S ;

Yamakawa, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (11) :6384-6389

[44] Mutations in EFHC1 cause juvenile myoclonic epilepsy [J].

Suzuki, T ;

Delgado-Escueta, AV ;

Aguan, K ;

Alonso, ME ;

Shi, J ;

Hara, Y ;

Nishida, M ;

Numata, T ;

Medina, MT ;

Takeuchi, T ;

Morita, R ;

Bai, DS ;

Ganesh, S ;

Sugimoto, Y ;

Inazawa, J ;

Bailey, JN ;

Ochoa, A ;

Jara-Prado, A ;

Rasmussen, A ;

Ramos-Peek, J ;

Cordova, S ;

Rubio-Donnadieu, F ;

Inoue, Y ;

Osawa, M ;

Kaneko, S ;

Oguni, H ;

Mori, Y ;

Yamakawa, K .

NATURE GENETICS, 2004, 36 (08) :842-849

[45] Genetic association studies in epilepsy: "The truth is out there" [J].

Tan, NCK ;

Mulley, JC ;

Berkovic, SF .

EPILEPSIA, 2004, 45 (11) :1429-1442

[46] A bias-ed assessment of the use of SNPs in human complex traits [J].

Terwilliger, JD ;

Haghighi, F ;

Hiekkalinna, TS ;

Göring, HH .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (06) :726-734

[47] A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity [J].

Urak, Lydia ;

Feucht, Martha ;

Fathi, Nahid ;

Hornik, Kurt ;

Fuchs, Karoline .

HUMAN MOLECULAR GENETICS, 2006, 15 (16) :2533-2541

[48] Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel [J].

Vitko, I ;

Chen, YC ;

Arias, JM ;

Shen, Y ;

Wu, XR ;

Perez-Reyes, E .

JOURNAL OF NEUROSCIENCE, 2005, 25 (19) :4844-4855

[49] Sodium channel α1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms [J].

Wallace, RH ;

Hodgson, BL ;

Grinton, BE ;

Gardiner, RM ;

Robinson, R ;

Rodriguez-Casero, V ;

Sadleir, L ;

Morgan, J ;

Harkin, LA ;

Dibbens, LM ;

Yamamoto, T ;

Andermann, E ;

Mulley, JC ;

Berkovic, SF ;

Scheffer, IE .

NEUROLOGY, 2003, 61 (06) :765-769

[50] Generalized epilepsy with febrile seizures plus:: Mutation of the sodium channel subunit SCN1B [J].

Wallace, RH ;

Scheffer, IE ;

Parasivam, G ;

Barnett, S ;

Wallace, GB ;

Sutherland, GR ;

Berkovic, SF ;

Mulley, JC .

NEUROLOGY, 2002, 58 (09) :1426-1429

← 1 2 3 4 5 6 →