PTPN11base
Database for several diseases
(Noonan syndrome, Noonan-like / multiple giant-cell lesion syndrome and Juvenile myelomonocytic leukaemia)

 Version 1.00 last updated 28 February, 2007 - contains 251 public entries


Curators: Mauno Vihinen
Maintained by Ilkka Lappalainen


SH2base

IMT Bioinformatics

Short description of the PTPN11base:

The PTPN11 gene encodes SHP-2, a cytoplasmic tyrosine phosphatase that consists of two tandemly arranged SH2 domains at the N-terminus, a catalytic domain, and a C-terminal tail. SHP-2 is a critical component in several signalling pathways involved in the control of developmental processes, hematopoiesis, and metabolism. Mutations in PTPN11 cause Noonan syndrome (NS), a developmental disorder characterized by facial dysmorphisms, short stature, skeletal and haematological defects, and cardiovascular abnormalities. Leopard sydrome (LS), a clinically related disorder, is caused by mutations in the SHP-2 catalytic domain. PTPN11 mutations also occur in several human cancers, including juvenile myelomonocytic leukaemia (JMML), myelodysplastic syndrome (MDS), B-cell acute lymphoblastic leukaemia (BLL), and acute myelogeneous leukaemia (AML). The activating PTPN11 mutations play a broad role in cancer, because SHP-2 acts as a signal-enhancing signalling component in pathways that regulate cell growth, transformation, differentiation, and migration. The protein is also required for normal Ras activation in many of these pathways.

OMIM resources:

151100
163950
163955
607785
176876

PTPN11base mutation publications:

Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C, Fazio VM, Di Ciommo V, Marino B, Pizzuti A, Dallapiccola B. Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes. J Med Genet. 2003 Sep;40(9):704-8.

Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002 Jun;70(6):1555-63.

Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A. Genotype-phenotype correlations in Noonan syndrome. J Pediatr. 2004 Mar;144(3):368-74.

Musante L, Kehl HG, Majewski F, Meinecke P, Schweiger S, Gillessen-Kaesbach G, Wieczorek D, Hinkel GK, Tinschert S, Hoeltzenbein M, Ropers HH, Kalscheuer VM. Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. Eur J Hum Genet. 2003 Feb;11(2):201-6.

Tartaglia M, Martinelli S, Cazzaniga G, Cordeddu V, Iavarone I, Spinelli M, Palmi C, Carta C, Pession A, Aricò M, Masera G, Basso G, Sorcini M, Gelb BD, Biondi A. Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood. 2004 Jul 15;104(2):307-13.

Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD, Gelb BD. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet. 2003 Jun;34(2):148-50.

Kratz CP, Niemeyer CM, Castleberry RP, Cetin M, Bergsträsser E, Emanuel PD, Hasle H, Kardos G, Klein C, Kojima S, Stary J, Trebo M, Zecca M, Gelb BD, Tartaglia M, Loh ML. The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood. 2005 Sep 15;106(6):2183-5.

Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM. Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood. 2004 Mar 15;103(6):2325-31.

Maheshwari M, Belmont J, Fernbach S, Ho T, Molinari L, Yakub I, Yu F, Combes A, Towbin J, Craigen WJ, Gibbs R. PTPN11 mutations in Noonan syndrome type I: detection of recurrent mutations in exons 3 and 13. Hum Mutat. 2002 Oct;20(4):298-304.

Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001 Dec;29(4):465-8.

Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T. PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. J Clin Endocrinol Metab. 2002 Aug;87(8):3529-33.

Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A. Genotype-phenotype correlations in Noonan syndrome. J Pediatr. 2004 Mar;144(3):368-74. Schollen E, Matthijs G, Gewillig M, Fryns JP, Legius E. PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning. Eur J Hum Genet. 2003 Jan;11(1):85-8.

Jafarov T, Ferimazova N, Reichenberger E. Noonan-like syndrome mutations in PTPN11 in patients diagnosed with cherubism. Clin Genet. 2005 Aug;68(2):190-1.

Legius E, Schrander-Stumpel C, Schollen E, Pulles-Heintzberger C, Gewillig M, Fryns JP. PTPN11 mutations in LEOPARD syndrome. J Med Genet. 2002 Aug;39(8):571-4.

Digilio MC, Pacileo G, Sarkozy A, Limongelli G, Conti E, Cerrato F, Marino B, Pizzuti A, Calabrò R, Dallapiccola B. Familial aggregation of genetically heterogeneous hypertrophic cardiomyopathy: a boy with LEOPARD syndrome due to PTPN11 mutation and his nonsyndromic father lacking PTPN11 mutations. Birth Defects Res A Clin Mol Teratol. 2004 Feb;70(2):95-8.

Matsubara K, Yabe H, Ogata T, Yoshida R, Fukaya T. Acute myeloid leukemia in an adult Noonan syndrome patient with PTPN11 mutation. Am J Hematol. 2005 Jun;79(2):171-2.

Conti E, Dottorini T, Sarkozy A, Tiller GE, Esposito G, Pizzuti A, Dallapiccola B. A novel PTPN11 mutation in LEOPARD syndrome. Hum Mutat. 2003 Jun;21(6):654.

 

 

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