leopard syndrome

Summary

Summary: An autosomal dominant disorder with an acronym of its seven features (LENTIGO; ELECTROCARDIOGRAM abnormalities; ocular HYPERTELORISM; PULMONARY STENOSIS; abnormal genitalia; retardation of growth; and DEAFNESS or SENSORINEURAL HEARING LOSS). This syndrome is caused by mutations of PTPN11 gene encoding the non-receptor PROTEIN TYROSINE PHOSPHATASE, type 11, and is an allelic to NOONAN SYNDROME. Features of LEOPARD syndrome overlap with those of NEUROFIBROMATOSIS 1 which is caused by mutations in the NEUROFIBROMATOSIS 1 GENES.

Top Publications

  1. Digilio M, Sarkozy A, Pacileo G, Limongelli G, Marino B, Dallapiccola B. PTPN11 gene mutations: linking the Gln510Glu mutation to the "LEOPARD syndrome phenotype". Eur J Pediatr. 2006;165:803-5 pubmed
    We describe the "LEOPARD syndrome (LS) phenotype" associated with the Gln510Glu mutation of the PTPN11 gene in two patients presenting with rapidly progressive severe biventricular obstructive hypertrophic cardiomyopathy and ..
  2. Sarkozy A, Digilio M, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis. 2008;3:13 pubmed publisher
    b>LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies...
  3. Sarkozy A, Conti E, Digilio M, Marino B, Morini E, Pacileo G, et al. Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. J Med Genet. 2004;41:e68 pubmed
  4. Carcavilla A, Pinto I, Muñoz Pacheco R, Barrio R, Martín Frías M, Ezquieta B. LEOPARD syndrome (PTPN11, T468M) in three boys fulfilling neurofibromatosis type 1 clinical criteria. Eur J Pediatr. 2011;170:1069-74 pubmed publisher
    ..Both NS and NFNS display phenotypic overlapping with LEOPARD syndrome (LS), and differential diagnosis between these two entities often represents a challenge for clinicians...
  5. Hanna N, Montagner A, Lee W, Miteva M, Vidal M, Vidaud M, et al. Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Lett. 2006;580:2477-82 pubmed
    ..In transfected cells stimulated with epidermal growth factor, the least active LS mutants promote Gab1/PI3K binding, validating our in vitro data. LS mutants thus display a reduced PTP activity both in vitro and in transfected cells...
  6. Carvajal Vergara X, Sevilla A, D Souza S, Ang Y, Schaniel C, Lee D, et al. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature. 2010;465:808-12 pubmed publisher
    ..We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular ..
  7. Laux D, Kratz C, Sauerbrey A. Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome. J Pediatr Hematol Oncol. 2008;30:602-4 pubmed publisher
    Germline mutations in PTPN11 gene cause Noonan syndrome and the clinically similar LEOPARD syndrome (LS)...
  8. Oishi K, Zhang H, Gault W, Wang C, Tan C, Kim I, et al. Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development. Hum Mol Genet. 2009;18:193-201 pubmed publisher
  9. Du Thanh A, Cave H, Bessis D, Puso C, Guilhou J, Dereure O. A novel PTPN11 gene mutation in a patient with LEOPARD Syndrome. Arch Dermatol. 2007;143:1210-1 pubmed

More Information

Publications82

  1. Beier A, Barrett R, Burke K, Kole B, Soo T. Leopard syndrome and Chiari type I malformation: a case report and review of the literature. Neurologist. 2009;15:37-9 pubmed publisher
    The authors present a 31-year-old man with a Chiari type I malformation (CM-1) occurring in conjunction with LEOPARD syndrome. He presented with severe dysphagia requiring placement of a percutaneous endoscopic gastrostomy (PEG) tube...
  2. Pandit B, Sarkozy A, Pennacchio L, Carta C, Oishi K, Martinelli S, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007;39:1007-12 pubmed
    ..SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases...
  3. Edouard T, Combier J, Nédélec A, Bel Vialar S, Métrich M, Conte Auriol F, et al. Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling. Mol Cell Biol. 2010;30:2498-507 pubmed publisher
    b>LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). How these alterations cause the disease remains unknown...
  4. Ucar C, Calýskan U, Martini S, Heinritz W. Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). J Pediatr Hematol Oncol. 2006;28:123-5 pubmed
    The LEOPARD syndrome is a complex of multisystemic congenital abnormalities characterized by lentiginosis, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of ..
  5. Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet. 2006;78:279-90 pubmed
    ..gene encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (NS) and the clinically related LEOPARD syndrome (LS), whereas somatic mutations in the same gene contribute to leukemogenesis...
  6. Conti E, Dottorini T, Sarkozy A, Tiller G, Esposito G, Pizzuti A, et al. A novel PTPN11 mutation in LEOPARD syndrome. Hum Mutat. 2003;21:654 pubmed
    PTPN11 gene mutations are common to both patients with Noonan (NS) and LEOPARD syndrome (LS). So far only two recurrent mutations have been identified in LS patients by different research groups, i.e., Tyr279Cys and Thr468Met...
  7. Marin T, Keith K, Davies B, Conner D, Guha P, Kalaitzidis D, et al. Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation. J Clin Invest. 2011;121:1026-43 pubmed publisher
    b>LEOPARD syndrome (LS) is an autosomal dominant "RASopathy" that manifests with congenital heart disease...
  8. Kalidas K, Shaw A, Crosby A, Newbury Ecob R, Greenhalgh L, Temple I, et al. Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J Hum Genet. 2005;50:21-5 pubmed
    b>LEOPARD syndrome (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) is an autosomal dominant condition...
  9. Reinker K, Stevenson D, Tsung A. Orthopaedic conditions in Ras/MAPK related disorders. J Pediatr Orthop. 2011;31:599-605 pubmed publisher
    The RAS/MAPK disorders [Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, and Leopard syndrome] are heterogenous conditions with phenotypic overlap...
  10. Yu Z, Xu J, Walls C, Chen L, Zhang S, Zhang R, et al. Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations. J Biol Chem. 2013;288:10472-82 pubmed publisher
    ..Interestingly, Noonan syndrome SHP2 mutants are constitutively active, whereas LEOPARD syndrome SHP2 mutants exhibit reduced phosphatase activity...
  11. Kontaridis M, Swanson K, David F, Barford D, Neel B. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006;281:6785-92 pubmed
    Multiple lentigines/LEOPARD syndrome (LS) is a rare, autosomal dominant disorder characterized by Lentigines, Electrocardiogram abnormalities, Ocular hypertelorism, Pulmonic valvular stenosis, Abnormalities of genitalia, Retardation of ..
  12. Bonetti M, Paardekooper Overman J, Tessadori F, Noël E, Bakkers J, den Hertog J. Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. Development. 2014;141:1961-70 pubmed publisher
    Germline mutations in PTPN11, encoding Shp2, cause Noonan syndrome (NS) and LEOPARD syndrome (LS), two developmental disorders that are characterized by multiple overlapping symptoms...
  13. Limongelli G, Sarkozy A, Pacileo G, Calabro P, Digilio M, Maddaloni V, et al. Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. Am J Med Genet A. 2008;146A:620-8 pubmed publisher
    Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (..
  14. Jopling C, van Geemen D, den Hertog J. Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects. PLoS Genet. 2007;3:e225 pubmed
    ..We generated mutants of Shp2 with mutations that were identified in human patients with Noonan or LEOPARD Syndrome and established that Noonan Shp2 was activated and LEOPARD Shp2 lacked catalytic protein-tyrosine phosphatase ..
  15. Seishima M, Mizutani Y, Shibuya Y, Arakawa C, Yoshida R, Ogata T. Malignant melanoma in a woman with LEOPARD syndrome: identification of a germline PTPN11 mutation and a somatic BRAF mutation. Br J Dermatol. 2007;157:1297-9 pubmed
  16. Sarkozy A, Obregon M, Conti E, Esposito G, Mingarelli R, Pizzuti A, et al. A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. Eur J Hum Genet. 2004;12:1069-72 pubmed
    ..This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders...
  17. Limongelli G, Pacileo G, Marino B, Digilio M, Sarkozy A, Elliott P, et al. Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. Am J Cardiol. 2007;100:736-41 pubmed
    The aim of this study was to characterize cardiovascular involvement in a large number of patients with LEOPARD syndrome. Twenty-six patients (age range 0 to 63 years, median age at the time of the study evaluation 17 years) underwent ..
  18. Keren B, Hadchouel A, Saba S, Sznajer Y, Bonneau D, Leheup B, et al. PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. J Med Genet. 2004;41:e117 pubmed
  19. Sarkozy A, Schirinzi A, Lepri F, Bottillo I, De Luca A, Pizzuti A, et al. Clinical lumping and molecular splitting of LEOPARD and NF1/NF1-Noonan syndromes. Am J Med Genet A. 2007;143A:1009-11 pubmed
  20. Digilio M, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R, et al. LEOPARD syndrome: clinical diagnosis in the first year of life. Am J Med Genet A. 2006;140:740-6 pubmed
    b>LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, ..
  21. Stewart R, Sanda T, Widlund H, Zhu S, Swanson K, Hurley A, et al. Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis. Dev Cell. 2010;18:750-62 pubmed publisher
    ..Paradoxically, Noonan syndrome mutations increase SHP2 phosphatase activity, while LEOPARD syndrome mutants are catalytically impaired, raising the possibility that SHP2 has phosphatase-independent roles...
  22. Antunes M, Arteaga E, Matsumoto A, Ianni B. Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death. Arq Bras Cardiol. 2009;92:e44-6, e71-3 pubmed
    We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention...
  23. Kang H, Bahadoran P, Ortonne J. Reflectance confocal microscopy for pigmentary disorders. Exp Dermatol. 2010;19:233-9 pubmed publisher
    ..The great advantages of non-invasive and repetitive examination of RCM may provide its usefulness not only in the diagnosis and management of pigmentary disorders, but also in researching pathogenesis of pigmentary disorders. ..
  24. Roubertoux P, de Vries P. From molecules to behavior: lessons from the study of rare genetic disorders. Behav Genet. 2011;41:341-8 pubmed publisher
    ..Finally, rare diseases have shed new light on the strengths and weaknesses of animal models in the study of behavioural phenotypes...
  25. Iwasaki Y, Horigome H, Takahashi Igari M, Kato Y, Razzaque M, Matsuoka R. Coronary artery dilatation in LEOPARD syndrome. A child case and literature review. Congenit Heart Dis. 2009;4:38-41 pubmed publisher
    b>LEOPARD syndrome (LS) is a rare inherited disease with multiple somatic abnormalities. LS and Noonan syndrome (NS) share many features, including cardiovascular disorders, and PTPN11 gene mutation is commonly reported in both syndromes...
  26. Porciello R, Divona L, Strano S, Carbone A, Calvieri C, Giustini S. Leopard syndrome. Dermatol Online J. 2008;14:7 pubmed
    ..A diagnosis of LEOPARD syndrome may be established exclusively on the basis of clinical criteria...
  27. Cetinkaya E, Gunal N, Sönmez N, Aycan Z, Vidinlisan S, Kahramanyol O, et al. LEOPARD syndrome and hypertrophic obstructive cardiomyopathy: a case report. Turk J Pediatr. 2004;46:373-6 pubmed
    The LEOPARD syndrome is a rare, autosomal dominant multisystemic disorder characterized by lentiginosis, ocular hypertelorism, abnormal genitalia, growth retardation, sensorineural deafness, and cardiac and electrocardiographic ..
  28. Fryer A. Mucosal lesions can occur in leopard syndrome. Clin Dysmorphol. 2007;16:277-8 pubmed
  29. Quatrano N, Loechner K. Dermatologic manifestations of endocrine disorders. Curr Opin Pediatr. 2012;24:487-93 pubmed publisher
    ..Conversely, when these associated signs go undetected or misdiagnosed, therapeutic intervention may be delayed unnecessarily. ..
  30. Tartaglia M, Gelb B, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25:161-79 pubmed publisher
    ..Here, we provide an overview of clinical aspects of this disorder and closely related conditions, the molecular mechanisms underlying pathogenesis, and major genotype-phenotype correlations. ..
  31. Hasle H. Malignant diseases in Noonan syndrome and related disorders. Horm Res. 2009;72 Suppl 2:8-14 pubmed publisher
    The overall risk of cancer in children with Noonan (NS), cardio-facial-cutaneous, Costello or LEOPARD syndrome is high, although no precise estimates are available...
  32. Rodríguez Bujaldon A, Vazquez Bayo C, Jimenez Puya R, Galan Gutierrez M, Moreno Gimenez J, Rodriguez Garcia A, et al. LEOPARD syndrome: what are café noir spots?. Pediatr Dermatol. 2008;25:444-8 pubmed publisher
  33. Massoure P, Latremouille C, Lamblin G, Leca F. LEOPARD syndrome. Cardiovasc J Afr. 2012;23:e19-20 pubmed publisher
    b>LEOPARD syndrome (LS) is a rare hereditary disorder, characterised mainly by skin, facial and cardiac abnormalities. We report on the case of a six-year-old Djiboutian with typical features of LS...
  34. Koudova M, Seemanova E, Zenker M. Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence. Eur J Med Genet. 2009;52:337-40 pubmed publisher
    ..We report on a patient with LEOPARD syndrome and normal intelligence who was found to carry a novel sequence change in BRAF. The mutation p...
  35. Digilio M, Capolino R, Marino B, Sarkozy A, Dallapiccola B. Congenital intrahepatic portosystemic venous shunt: an unusual feature in LEOPARD syndrome and in neurofibromatosis type 1. Am J Med Genet A. 2005;134:457-8 pubmed
  36. Kleefstra T, Wortmann S, Rodenburg R, Bongers E, Hadzsiev K, Noordam C, et al. Mitochondrial dysfunction and organic aciduria in five patients carrying mutations in the Ras-MAPK pathway. Eur J Hum Genet. 2011;19:138-44 pubmed publisher
    ..We postulate that patients with Ras-MAPK mutations have an increased susceptibility, but a second metabolic hit is needed to cause the clinical manifestation of mitochondrial dysfunction. ..
  37. Singh S, Zech A, Geertz B, Reischmann Düsener S, Osinska H, Prondzynski M, et al. Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3-Targeted Knockin Mice. Circ Heart Fail. 2017;10: pubmed publisher
    ..autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM ..
  38. Schramm C, Edwards M, Krenz M. New approaches to prevent LEOPARD syndrome-associated cardiac hypertrophy by specifically targeting Shp2-dependent signaling. J Biol Chem. 2013;288:18335-44 pubmed publisher
    In LEOPARD syndrome (LS) patients, mutations in the protein tyrosine phosphatase Shp2 cause hypertrophic cardiomyopathy...
  39. Wakabayashi Y, Yamazaki K, Narumi Y, Fuseya S, Horigome M, Wakui K, et al. Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His. Am J Med Genet A. 2011;155A:2529-33 pubmed publisher
    b>LEOPARD syndrome (LS), generally caused by heterozygous mutations in the PTPN11 gene, is a rare autosomal-dominant multiple congenital anomaly condition, characterized by skin, facial, and cardiac abnormalities...
  40. Noonan J. Noonan syndrome and related disorders: alterations in growth and puberty. Rev Endocr Metab Disord. 2006;7:251-5 pubmed
    ..This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis. ..
  41. Bertola D, Pereira A, Albano L, de Oliveira P, Kim C, Krieger J. PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype. Genet Test. 2006;10:186-91 pubmed
    ..Fifty probands with Noonan syndrome ascertained according to well-established diagnostic criteria, 3 with LEOPARD syndrome, 5 with Noonan-like/multiple giant cell lesion syndrome, and 3 with neurofibromatosis/ Noonan were enrolled ..
  42. Seibt C, Flender B, Gutberlet M. Comprehensive non-invasive pre-surgical magnetic resonance imaging in a patient with LEOPARD's syndrome cardiomyopathy. Eur Heart J. 2006;27:1407 pubmed
  43. Ogata T, Yoshida R. PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes. Pediatr Endocrinol Rev. 2005;2:669-74 pubmed
    ..phosphatase, nonreceptor type 11) mutations and genotype-phenotype correlations in Noonan syndrome (NS) and LEOPARD syndrome (LS). PTPN11 mutations have been identified in approximately 40% of NS patients and in >80% of LS patients...
  44. Piard J, Verloes A, Cave H, Peuchmaur M, Bennaceur S, LeHeup B. Extensive abdominal lipomatosis in a patient with Noonan/LEOPARD syndrome (Noonan syndrome-Multiple Lentigines). Am J Med Genet A. 2012;158A:1406-10 pubmed publisher
    ..1517A > C-p.Gln506Pro in the PTPN11 gene. The patient developed an unusual extensive lipomatosis and we discuss possible relationship between her lipomatosis and NS...
  45. Simsek Kiper P, Alanay Y, Gulhan B, Lissewski C, Türkyilmaz D, Alehan D, et al. Clinical and molecular analysis of RASopathies in a group of Turkish patients. Clin Genet. 2013;83:181-6 pubmed publisher
    ..Our findings indicate that molecular epidemiology and genotype-phenotype correlations in RASopathies are relatively independent from the ethnic population background...
  46. Ishigami T, Wakamatsu A, Kishida T, Yokoyama K, Sugiyama K. [ECG changes during emergence from anesthesia in a patient with LEOPARD syndrome]. Masui. 2003;52:1115-7 pubmed
    b>LEOPARD syndrome is a rare congenital disease characterized by seven features. Besides the original clinical manifestations, hypertrophic cardiomyopathy was reported as an additional laboratory finding recently...
  47. Sorgel F, Thyroff Friesinger U, Vetter A, Vens Cappell B, Kinzig M. Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial. BMC Clin Pharmacol. 2009;9:10 pubmed publisher
  48. Cerrato F, Pacileo G, Limongelli G, Gagliardi M, Santoro G, Digilio M, et al. A standard echocardiographic and tissue Doppler study of morphological and functional findings in children with hypertrophic cardiomyopathy compared to those with left ventricular hypertrophy in the setting of Noonan and LEOPARD syndromes. Cardiol Young. 2008;18:575-80 pubmed publisher
    ..Less is known regarding morphological and functional characteristics of the left ventricular hypertrophy found in the setting of the Noonan and LEOPARD syndromes...
  49. Conboy E, Dhamija R, Wang M, Xie J, Dyck P, Bridges A, et al. Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. J Med Genet. 2016;53:123-6 pubmed publisher
    Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth ..
  50. Digilio M, Pacileo G, Sarkozy A, Limongelli G, Conti E, Cerrato F, et al. 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;70:95-8 pubmed
    ..Multiple chromosomal loci have been found to be involved in the etiology of this defect. LEOPARD syndrome is a genetic condition characteristically associated with HCM...
  51. Rankin J, Short J, Turnpenny P, Castle B, Hanemann C. Medulloblastoma in a patient with the PTPN11 p.Thr468Met mutation. Am J Med Genet A. 2013;161A:2027-9 pubmed publisher
    ..pathway which include Noonan syndrome, Noonan syndrome with multiple lentigines (NSML; formerly called LEOPARD syndrome), Costello syndrome, Cardiofaciocutaneous syndrome, Legius syndrome, and Neurofibromatosis type 1 (NF1), ..
  52. Chan G, Kalaitzidis D, Neel B. The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev. 2008;27:179-92 pubmed publisher
    ..Elucidation of the events underlying Shp2-evoked transformation may provide new insights into oncogenic mechanisms and novel targets for anti-cancer therapy...
  53. Kalev I, Muru K, Teek R, Zordania R, Reimand T, Köbas K, et al. LEOPARD syndrome with recurrent PTPN11 mutation Y279C and different cutaneous manifestations: two case reports and a review of the literature. Eur J Pediatr. 2010;169:469-73 pubmed publisher
    b>LEOPARD syndrome (LS) is a heterogeneous disease characterised mainly by cutaneous manifestations...
  54. Schubbert S, Bollag G, Shannon K. Deregulated Ras signaling in developmental disorders: new tricks for an old dog. Curr Opin Genet Dev. 2007;17:15-22 pubmed
    ..Many of these germline, disease-associated mutations encode novel Ras, Raf and MEK proteins. These studies underscore a crucial role of Ras signaling in human development...
  55. Watanabe Y, Yano S, Niihori T, Aoki Y, Matsubara Y, Yoshino M, et al. A familial case of LEOPARD syndrome associated with a high-functioning autism spectrum disorder. Brain Dev. 2011;33:576-9 pubmed publisher
    A connection between LEOPARD syndrome (a rare autosomal dominant disorder) and autism spectrum disorders (ASDs) may exist...
  56. Alfieri P, Cesarini L, Mallardi M, Piccini G, Caciolo C, Leoni C, et al. Long term memory profile of disorders associated with dysregulation of the RAS-MAPK signaling cascade. Behav Genet. 2011;41:423-9 pubmed publisher
    ..evaluated long term memory in twenty individuals with molecularly confirmed diagnosis of Noonan syndrome and LEOPARD syndrome, two disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling ..
  57. Bessis D. [Neuro-cardio-facial-cutaneous syndrome]. Ann Dermatol Venereol. 2011;138:483-93 pubmed publisher
    ..NCFC subsumes neurofibromatosis type1, Legius syndrome, LEOPARD syndrome, Noonan syndrome, Costello syndrome and cardiofaciocutaneous (CFC) syndrome...
  58. Santoro C, Pacileo G, Limongelli G, Scianguetta S, Giugliano T, Piluso G, et al. LEOPARD syndrome: clinical dilemmas in differential diagnosis of RASopathies. BMC Med Genet. 2014;15:44 pubmed publisher
    ..Here, we describe a child initially diagnosed with Neurofibromatosis-Noonan syndrome. The follow-up of the proband, the clinical evaluation of his father together with a gene-by-gene testing approach led us to the proper diagnosis...
  59. Kuburović V, Vukomanovic V, Carcavilla A, Ezquieta Zubicaray B, Kuburović N. Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children. Turk J Pediatr. 2011;53:687-91 pubmed
    b>LEOPARD syndrome 2 (LS-2) (OMIM #611554) is a rare, dominantly inherited genetic disorder affecting multiple organ systems...
  60. Goyal S, Aragam J. Aortic root dilatation with redundancy of mitral and aortic leaflets associated with the LEOPARD syndrome. Int J Cardiol. 2006;110:110-1 pubmed
  61. Lin B, Kim J, Li Y, Pan H, Carvajal Vergara X, Salama G, et al. High-purity enrichment of functional cardiovascular cells from human iPS cells. Cardiovasc Res. 2012;95:327-35 pubmed publisher
    ..In the present study, a highly reproducible method was developed that can simultaneously enrich a large number of CMs and cardiac SMCs and ECs from human induced pluripotent stem (iPS) cells with high purity...
  62. Liang J, Chien Y, Hwu W, Yeh S, Peng S. Schizencephaly in LEOPARD syndrome. Pediatr Neurol. 2009;41:71-3 pubmed publisher
    ..The presence of LEOPARD syndrome was confirmed by a genetic study and clinical phenotypes...
  63. Hammerstingl C, Ghanem A, Tiemann K. An unusual cause for recurrent syncope in a female adult with LEOPARD syndrome. Echocardiography. 2009;26:596-7 pubmed publisher
    The LEOPARD syndrome is a rare autosomal dominant, multisystem disease involving the skin, skeletal and cardiovascular systems...
  64. Torres J, Russo P, Tobias J. Anaesthetic implications of LEOPARD syndrome. Paediatr Anaesth. 2004;14:352-6 pubmed
    b>LEOPARD syndrome is a neuroectodermal disorder presumed to result from an abnormality in neural crest cells...
  65. Paradisi M, Pedicelli C, Ciasulli A, Pinto F, Conti E, Sarkozy A, et al. [PTPN11 gene mutation in LEOPARD syndrome]. Minerva Pediatr. 2005;57:189-93 pubmed
    The multiple lentigines/LEOPARD syndrome (ML/LS) is a rare and complex genetic syndrome. It is an autosomal dominant disorder with a variable expressivity...
  66. Hansen L, Risby K, Bygum A, Gerdes A. [LEOPARD syndrome]. Ugeskr Laeger. 2009;171:247 pubmed
    We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome (LS). The diagnosis was confirmed in the boy and his mother, who both had a mutation in the PTPN11 gene at Thr468Met (c.1403C > T)...
  67. Kato H, Yoshida R, Tsukamoto K, Suga H, Eto H, Higashino T, et al. Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome). Int J Dermatol. 2010;49:1146-51 pubmed publisher
    ..These findings sufficed to fulfill the criteria for LEOPARD syndrome (multiple lentigines syndrome), although they lacked five of seven major clinical features...
  68. Demir S, Karakaya Z, Sagay S. A rare cause of dyspnoea: the LEOPARD syndrome. J Pak Med Assoc. 2013;63:527-9 pubmed
    The LEOPARD syndrome is a rare hereditary disorder in Asian countries. This syndrome involves complex malformations and other features...
  69. Tang S, Hoshida H, Kamisago M, Yagi H, Momma K, Matsuoka R. Phenotype-genotype correlation in a patient with co-occurrence of Marfan and LEOPARD syndromes. Am J Med Genet A. 2009;149A:2216-9 pubmed publisher
    ..Y279C change in PTPN11 rather than the mutation in FBN1. To our knowledge, this is the first report of mutations in both FBN1 and PTPN11 with combined phenotypes of Marfan and LEOPARD syndromes...
  70. Dhandapany P, Fabris F, Tonk R, Illaste A, Karakikes I, Sorourian M, et al. Cyclosporine attenuates cardiomyocyte hypertrophy induced by RAF1 mutants in Noonan and LEOPARD syndromes. J Mol Cell Cardiol. 2011;51:4-15 pubmed publisher
    ..rat cardiomyocytes (NRCMs and ARCMs, respectively) with adenoviruses encoding wild-type RAF1 and three Noonan/LEOPARD syndrome-associated RAF1 mutants (S257L, D486N or L613V)...
  71. Ishida H, Kogaki S, Narita J, Ichimori H, Nawa N, Okada Y, et al. LEOPARD-type SHP2 mutant Gln510Glu attenuates cardiomyocyte differentiation and promotes cardiac hypertrophy via dysregulation of Akt/GSK-3?/?-catenin signaling. Am J Physiol Heart Circ Physiol. 2011;301:H1531-9 pubmed publisher
    b>LEOPARD syndrome (LS) is an autosomal dominant inherited multisystemic disorder. Most cases involve mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Src homology 2-containing protein phosphatase 2 (SHP2)...
  72. Onesti M, Fioramonti P, Fino P, Carella S, Spinelli G, Miraglia E, et al. An uncommon association between skin lesions and LEOPARD syndrome affected an old patient. Case report. Ann Ital Chir. 2011;82:79-82 pubmed
    b>LEOPARD syndrome (LS) is a rare inherited autosomal dominant disease with high penetrance and markedly variable expression characterized by a spectrum of somatic abnormalities...