Defective Mitochondrial mRNA Maturation Is Associated with Spastic Ataxia

被引：61

作者：

Crosby, Andrew H. ^{[1
]}

Patel, Heema ^{[1
]}

Chioza, Barry A. ^{[1
]}

Proukakis, Christos ^{[1
,2
]}

Gurtz, Kay ^{[3
]}

Patton, Michael A. ^{[1
]}

Sharifi, Reza ^{[1
]}

Harlalka, Gaurav ^{[1
]}

Simpson, Michael A. ^{[1
]}

Dick, Katherine ^{[1
]}

Reed, Johanna A. ^{[1
]}

Al-Memar, Ali ^{[4
]}

Chrzanowska-Lightowlers, Zofia M. A. ^{[5
]}

Cross, Harold E. ^{[6
]}

Lightowlers, Robert N. ^{[5
]}

机构：

[1] St Georges Univ London, Ctr Med Genet, London SW17 0RE, England

[2] UCL, Dept Clin Neurosci, Inst Neurol, London NW3 2PT, England

[3] Windows Hope Genet Study, Geauga Cty, OH 44687 USA

[4] St George Hosp, Dept Neurol, London SW17 0RE, England

[5] Newcastle Univ, Sch Med, Mitochondrial Res Grp, Inst Ageing & Hlth, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[6] Univ Arizona, Sch Med, Dept Ophthalmol, Tucson, AZ 85711 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2010年 / 87卷 / 05期

基金：

英国生物技术与生命科学研究理事会;

关键词：

POLY(A) POLYMERASE; PARAPLEGIA; MUTATIONS;

D O I：

10.1016/j.ajhg.2010.09.013

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In human mitochondria, polyadenylation of mRNA undertaken by the nuclear encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression Our molecular investigation of an autosomal recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype When subjected to poly(A) tail length assays mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails Although defective mitochondrial DNA maintenance underlies a well described group of clinical disorders, our findings reveal a defect of mitochondrial mRNA maturation associated with human disease and imply that this disease mechanism should be considered in other complex neurodegenerative disorders

引用

页码：655 / 660

页数：6

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