Hurt, tired and queasy: Specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic "functional" symptomatology including pain, fatigue and gastrointestinal dysmotility

被引：11

作者：

Boles, Richard G. ^{[1
]}

Hornung, Holly A. ^{[1
]}

Moody, Alastair E. ^{[1
]}

Ortiz, Thomas B. ^{[1
]}

Wong, Stacey A. ^{[1
]}

Eggington, Julie M. ^{[1
]}

Stanley, Christine M. ^{[1
]}

Gao, Mu ^{[2
]}

Zhou, Hongyi ^{[2
]}

McLaughlin, Stephen ^{[1
]}

Zare, Amir S. ^{[1
]}

Sheldon, Katherine M. ^{[1
]}

Skolnick, Jeffrey ^{[2
]}

McKernan, Kevin J. ^{[1
]}

机构：

[1] Courtagen Life Sci, Woburn, MA 01801 USA

[2] Georgia Inst Technol, Ctr Study Syst Biol, Atlanta, GA 30318 USA

来源：

MITOCHONDRION | 2015年 / 23卷

基金：

美国国家卫生研究院;

关键词：

Autistic spectrum disorder; NextGen sequencing; Functional disease; Functional medicine; Protein chaperones; Computational protein analysis; TORSION DYSTONIA; PROTEIN; CRYSTALLIN; STRESS; DYT1;

D O I：

10.1016/j.mito.2015.05.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Functional disorders are common conditions with a substantial impact on a patients' wellbeing, and can be diagnostically elusive. There are bidirectional associations between functional disorders and mitochondrial dysfunction. In this study, provided clinical information and the exon sequence of the TRAP1 mitochondrial chaperone were retrospectively reviewed with a focus on the functional categories of chronic pain, fatigue and gastrointestinal dysmotility. Very-highly conserved TRAP1 variants were identified in 73 of 930 unrelated patients. Functional symptomatology is strongly associated with specific variants in the ATPase binding pocket In particular, the combined presence of all three functional categories is strongly associated with p.Ile253Val (OR 7.5, P = 0.0001) and with two other interacting variants (OR 18, P = 0.0005). Considering a 1-2% combined variant prevalence and high odds ratios, these variants may be an important factor in the etiology of functional symptomatology. (C) 2015 Elsevier B.V. and Mitochondria Research Society.

引用

页码：64 / 70

页数：7

共 1 条

[1] TIRED, HURTING, AND QUEASY: MUTATIONS IN THE MITOCHONDRIAL CHAPERONE TRAP1 ARE ASSOCIATED WITH COMMON FUNCTIONAL SYMPTOMATOLOGY AND ARE A NOVEL CAUSE OF POLYGENIC MITOCHONDRIAL DISEASE
Boles, Richard G.
Wong, Stacey A.
Hornung, Holly A.
Zare, Amir S.
Sheldon, Katherine M.
Foss, Ted R.
Stanley, Christine M.
McKernan, Kevin J.
MOLECULAR GENETICS AND METABOLISM, 2014, 111 (03) : 249 - 250

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