A Multiplex Human Syndrome Implicates a Key Role for Intestinal Cell Kinase in Development of Central Nervous, Skeletal, and Endocrine Systems

被引：58

作者：

Lahiry, Piya ^{[1
,2
]}

Wang, Jian ^{[2
]}

Robinson, John F. ^{[2
]}

Turowec, Jacob P. ^{[1
]}

Litchfield, David W. ^{[1
]}

Lanktree, Matthew B. ^{[1
,2
]}

Gloor, Gregory B. ^{[1
]}

Puffenberger, Erik G. ^{[3
]}

Strauss, Kevin A. ^{[3
]}

Martens, Mildred B. ^{[4
]}

Ramsay, David A. ^{[4
]}

Rupar, C. Anthony ^{[1
,5
,6
]}

Siu, Victoria ^{[1
,5
,6
]}

Hegele, Robert A. ^{[1
,2
]}

机构：

[1] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada

[2] Robarts Res Inst, London, ON N6A 5K8, Canada

[3] Clin Special Children, Strasburg, PA 17579 USA

[4] Univ Western Ontario Hosp, Dept Pathol, London Hlth Sci Ctr, London, ON N6A 5A5, Canada

[5] London Hlth Sci Ctr, Med Genet Program, London, ON N6C 2V5, Canada

[6] Childrens Hlth Res Inst, London, ON N6C 2V5, Canada

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 84卷 / 02期

基金：

加拿大健康研究院;

关键词：

RIB-POLYDACTYLY SYNDROME; HYDROLETHALUS SYNDROME; PROTEIN; IDENTIFICATION; MUTATIONS; MAJEWSKI; GENE; INHIBITORS; REGION;

D O I：

10.1016/j.ajhg.2008.12.017

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Six infants in an Old Order Amish pedigree were observed to be affected with endocrine-cerebro-osteodysplasia (ECO). ECO is a previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. Autozygosity mapping and sequencing identified a previously unknown missense mutation, R272Q, in ICK, encoding intestinal cell kinase (ICK). Our results established that R272 is conserved across species and among ethnicities, and three-dimensional analysis of the protein structure suggests protein instability due to the R272Q mutation. We also demonstrate that the R272Q mutant fails to localize at the nucleus and has diminished kinase activity. These findings suggest that ICK plays a key role in the development of

引用

页码：134 / 147

页数：14

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