Noonan syndrome and related disorders: genetics and pathogenesis.
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.
Tartaglia
Marco
M
Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, 299-00161 Rome, Italy. mtartaglia@iss.it
Gelb
Bruce D
BD
D000818:Animals; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D007938:Leukemia / Q000235:genetics; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D009634:Noonan Syndrome / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000266:history; D010331:Paternal Age; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse