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

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• 作者：Piya Lahiry ; Jian Wang ; John F. Robinson ; Jacob P. Turowec ; David W. Litchfield ; Matthew B. Lanktree ; Gregory B. Gloor ; Erik G. Puffenberger ; Kevin A. Strauss ; Mildred B. Martens ; David A. Ramsay ; C. Anthony Rupar ; Victoria Siu ; Robert A. Hegele
• 刊名：The American Journal of Human Genetics
• 出版年：2009
• 出版时间：13 February 2009
• 年：2009
• 卷：84
• 期：2
• 页码：134-147
• 全文大小：2094 K

文摘

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 multiple organ systems.