Noonan Syndrome and Related Disorders: Genetics and Pathogenesis.

Posted by rob on July 21, 2005 under Uncategorized | 2 Comments to Read

Tartaglia M, Gelb BD

Annu Rev Genomics Hum Genet. 2005 Apr 13;

Noonan syndrome is a pleiomorphic autosomal dominant disorder with short stature, facial dysmorphia, webbed neck, and heart defects. In the past decade, progress has been made in elucidating the pathogenesis of this disorder using a positional cloning approach. Noonan syndrome is now known to be a genetically heterogeneous disorder with nearly one half of cases caused by gain-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2. Similar germ line mutations cause two related genetic disorders, Noonan-like disorder with multiple giant cell lesion syndrome and LEOPARD syndrome, and somatic PTPN11 mutations can underlie certain pediatric hematopoietic malignancies, including juvenile myelomonocytic, acute lymphoblastic, and acute myelogenous leukemias. A mouse model of PTPN11-related Noonan syndrome was recently generated, providing a reagent for studying disease pathogenesis in greater depth as well as experimenting with novel therapeutic strategies. Expected online publication date for the Annual Review of Genomics and Human Genetics Volume 6 is August 30, 2005. Please see http://www.annualreviews.org/catalog/pub_dates.asp for revised estimates.

Noonan Syndrome and Related Disorders: Genetics and Pathogenesis.