TY - JOUR
T1 - Noonan syndrome and related disorders
T2 - Genetics and pathogenesis
AU - Tartaglia, Marco
AU - Gelb, Bruce D.
PY - 2005
Y1 - 2005
N2 - 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 pediatrie 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.
AB - 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 pediatrie 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.
KW - PTPN11
KW - SHP-2
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=18444401014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18444401014&partnerID=8YFLogxK
U2 - 10.1146/annurev.genom.6.080604.162305
DO - 10.1146/annurev.genom.6.080604.162305
M3 - Article
C2 - 16124853
AN - SCOPUS:18444401014
VL - 6
SP - 45
EP - 68
JO - Annual Review of Genomics and Human Genetics
JF - Annual Review of Genomics and Human Genetics
SN - 1527-8204
ER -