Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases

被引：21

作者：

Bagnall, Richard D. ^{[1
,2
]}

Crompton, Douglas E. ^{[3
,4
]}

Cutmore, Carina ^{[1
]}

Regan, Brigid M. ^{[3
]}

Berkovic, Samuel F. ^{[4
]}

Scheffer, Ingrid E. ^{[4
,5
,6
]}

Semsarian, Christopher ^{[1
,2
,7
]}

机构：

[1] Centenary Inst, Agnes Ginges Ctr Mol Cardiol, Sydney, NSW, Australia

[2] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia

[3] Northern Hlth, Dept Neurol, Melbourne, Vic, Australia

[4] Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Melbourne, Vic, Australia

[5] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

[6] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia

[7] Royal Prince Alfred Hosp, Dept Cardiol, Sydney, NSW, Australia

来源：

NEUROLOGY | 2014年 / 83卷 / 11期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

CENTRAL HYPOVENTILATION SYNDROME; MUTATIONS; FRAMESHIFT; EXPANSION; LENGTH;

D O I：

10.1212/WNL.0000000000000781

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To determine the contribution of sequence variations in PHOX2B to sudden unexpected death in epilepsy (SUDEP). Methods: Patients who died of SUDEP were identified in 2 major Australian cohorts, the Epilepsy Genetics research program in Melbourne and postmortem cases at the Department of Forensic Medicine in Sydney. Coding exons of the PHOX2B gene were sequenced and a fluorescent sizing assay was used to measure the PHOX2B polyalanine repeat sequence. Results: Sequencing of 68 cases of SUDEP identified a 15-nucleotide deletion in the PHOX2B polyalanine repeat region in one case, a 16-year-old adolescent with focal dyscognitive seizures from age 5 years. This deletion was verified using a fluorescent sizing assay. Two synonymous variants were identified in 4 cases, but no PHOX2B polyalanine repeat expansion alleles or point mutations were found. Conclusions: The absence of PHOX2B polyalanine repeat expansion alleles or point mutations in 68 Australian cases of SUDEP, with one deletion of uncertain significance, shows that PHOX2B mutations are not a common risk factor for SUDEP.

引用

页码：1018 / 1021

页数：4

共 13 条

[1] Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome [J].

Amiel, J ;

Laudier, B ;

Attié-Bitach, T ;

Trang, H ;

de Pontual, L ;

Gener, B ;

Trochet, D ;

Etchevers, H ;

Ray, P ;

Simonneau, M ;

Vekemans, M ;

Munnich, A ;

Gaultier, C ;

Lyonnet, S .

NATURE GENETICS, 2003, 33 (04) :459-461

[2] PHOX2B polyalanine repeat length is associated with sudden infant death syndrome and unclassified sudden infant death in the Dutch population [J].

Liebrechts-Akkerman, Germaine ;

Liu, Fan ;

Lao, Oscar ;

Ooms, Ariadne H. A. G. ;

van Duijn, Kate ;

Vermeulen, Mark ;

Jaddoe, Vincent W. ;

Hofman, Albert ;

Engelberts, Adele C. ;

Kayser, Manfred .

INTERNATIONAL JOURNAL OF LEGAL MEDICINE, 2014, 128 (04) :621-629

[3] Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study [J].

Ryvlin, Philippe ;

Nashef, Lina ;

Lhatoo, Samden D. ;

Bateman, Lisa M. ;

Bird, Jonathan ;

Bleasel, Andrew ;

Boon, Paul ;

Crespel, Arielle ;

Dworetzky, Barbara A. ;

Hogenhaven, Hans ;

Lerche, Holger ;

Maillard, Louis ;

Molter, Michael P. ;

Marchal, Cecile ;

Murthy, Jagarlapudi M. K. ;

Nitsche, Michael ;

Pataraia, Ekaterina ;

Rabben, Tede ;

Rheims, Sylvain ;

Sadzot, Bernard ;

Schulze-Bonhage, Andreas ;

Seyal, Masud ;

So, Elson L. ;

Spitz, Mark ;

Szucs, Anna ;

Tan, Meng ;

Tao, James X. ;

Tomson, Torbjorn .

LANCET NEUROLOGY, 2013, 12 (10) :966-977

[4]

Silvestri JM, 2000, PEDIATR PULM, V29, P351, DOI 10.1002/(SICI)1099-0496(200005)29:5<351::AID-PPUL3>3.0.CO

[5]

2-Z

[6] Sudden unexpected death in epilepsy: current knowledge and future directions [J].

Tomson, Torbjorn ;

Nashef, Lina ;

Ryvlin, Philippe .

LANCET NEUROLOGY, 2008, 7 (11) :1021-1031

[7] Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B [J].

Toyota, T ;

Yoshitsugu, K ;

Ebihara, M ;

Yamada, K ;

Ohba, H ;

Fukasawa, M ;

Minabe, Y ;

Nakamura, K ;

Sekine, Y ;

Takei, N ;

Suzuki, K ;

Itokawa, M ;

Meerabux, JMA ;

Iwayama-Shigeno, Y ;

Tomaru, Y ;

Shimizu, H ;

Hattori, E ;

Mori, N ;

Yoshikawa, T .

HUMAN MOLECULAR GENETICS, 2004, 13 (05) :551-561

[8] Molecular consequences of PHOX2B missense, frameshift and alanine expansion mutations leading to autonomic dysfunction [J].

Trochet, D ;

Hong, SJ ;

Lim, JK ;

Brunet, JF ;

Munnich, A ;

Kim, KS ;

Lyonnet, S ;

Goridis, C ;

Amiel, J .

HUMAN MOLECULAR GENETICS, 2005, 14 (23) :3697-3708

[9] PHOX2B germline and somatic mutations in late-onset central hypoventilation syndrome [J].

Trochet, Delphine ;

de Pontual, Loic ;

Straus, Christian ;

Gozal, David ;

Trang, Ha ;

Landrieu, Pierre ;

Munnich, Arnold ;

Lyonnet, Stanislas ;

Gaultier, Claude ;

Amiel, Jeanne .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 177 (08) :906-911

[10] Post-Mortem Review and Genetic Analysis of Sudden Unexpected Death in Epilepsy (SUDEP) Cases [J].

Tu, Emily ;

Bagnall, Richard D. ;

Duflou, Johan ;

Semsarian, Christopher .

BRAIN PATHOLOGY, 2011, 21 (02) :201-208

← 1 2 →