449 results match your criteria LEOPARD Syndrome


Melanoma in Noonan Syndrome With Multiple Lentigines (Leopard Syndrome): A New Case.

Actas Dermosifiliogr 2020 Jun 9. Epub 2020 Jun 9.

Servicio de Dermatología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, España.

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http://dx.doi.org/10.1016/j.ad.2019.01.017DOI Listing

[Noonan syndrome: genetic and clinical update and treatment options].

An Pediatr (Barc) 2020 May 31. Epub 2020 May 31.

Servicio de Endocrinología Pediátrica, Hospital Regional Universitario de Málaga, Málaga, España. Electronic address:

Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Read More

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http://dx.doi.org/10.1016/j.anpedi.2020.04.008DOI Listing
May 2020
0.722 Impact Factor

[LEOPARD syndrome].

Kardiologiia 2020 Mar 18;60(3):137-141. Epub 2020 Mar 18.

Russian Cardiology Research and Production Complex, Ministry of Health of Russia.

LEOPARD syndrome with multiple lentigines (cardiomyopathic lentiginosis) is a rare, genetically predetermined disease with autosomal dominant inheritance. Prevalence of this syndrome is unknown. One of pathognomonic clinical manifestations of this syndrome is the presence of multiple lentiginous pigment spots all over the body. Read More

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http://dx.doi.org/10.18087/cardio.2020.3.n944DOI Listing

P-Related Protein Accelerates Human Mesenchymal Stromal Cell Migration by Modulating VLA-5 Interactions with Fibronectin.

Cells 2020 Apr 29;9(5). Epub 2020 Apr 29.

Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9BQ, UK.

P-related protein (PZR), a Noonan and Leopard syndrome target, is a member of the transmembrane Immunoglobulin superfamily. Its cytoplasmic tail contains two immune-receptor tyrosine-based inhibitory motifs (ITIMs), implicated in adhesion-dependent signaling and regulating cell adhesion and motility. PZR promotes cell migration on the extracellular matrix (ECM) molecule, fibronectin, by interacting with SHP-2 (Src homology-2 domain-containing protein tyrosine phosphatase-2), a molecule essential for skeletal development and often mutated in Noonan and Leopard syndrome patients sharing overlapping musculoskeletal abnormalities and cardiac defects. Read More

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http://dx.doi.org/10.3390/cells9051100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290418PMC

CLOUDED LEOPARD () MORBIDITY AND MORTALITY IN CAPTIVE-BRED POPULATIONS: A COMPREHENSIVE RETROSPECTIVE STUDY OF MEDICAL DATA FROM 271 INDIVIDUALS IN EUROPEAN, ASIAN, AND AUSTRALIAN ZOOS.

J Zoo Wildl Med 2020 Mar;51(1):150-158

Unité de recherche EpiMAI (USC Anses), 94700 Maisons-Alfort, France.

The clouded leopard () is classified as vulnerable on the International Union for the Conservation of Nature Red List of Threatened Species. However, diseases affecting this species across zoo populations are not well documented. The primary objective of this retrospective study was to identify common and significant causes of morbidity and mortality in captive-bred clouded leopards from European, Asian, and Australian institutions. Read More

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http://dx.doi.org/10.1638/2019-0048DOI Listing

Images of the month 2: A leopard never changes its spots.

Clin Med (Lond) 2020 Mar;20(2):231-232

Kingston Hospital NHS Foundation Trust, Kingston upon Thames, UK.

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http://dx.doi.org/10.7861/clinmed.2019-0489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081801PMC

Design, synthesis, biological evaluation, common feature pharmacophore model and molecular dynamics simulation studies of ethyl 4-(phenoxymethyl)-2-phenylthiazole-5-carboxylate as Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors.

J Biomol Struct Dyn 2020 Feb 25:1-15. Epub 2020 Feb 25.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.

SHP2 is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell death pathway (PD-1/PD-L1) and cell growth and differentiation pathway (MAPK). Moreover, mutations in SHP2 have been implicated in Leopard syndrome (LS), Noonan syndrome (NS), juvenile myelomonocytic leukemia (JMML) and several types of cancer and solid tumors. Thus, SHP2 inhibitors are much needed reagents for evaluation of SHP2 as a therapeutic target. Read More

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http://dx.doi.org/10.1080/07391102.2020.1726817DOI Listing
February 2020

Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan.

Am J Med Genet A 2020 02 14;182(2):357-364. Epub 2019 Dec 14.

Department of Pediatrics and Rare Disease Center, Mackay Memorial Hospital, Taipei, Taiwan.

RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. Read More

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http://dx.doi.org/10.1002/ajmg.a.61429DOI Listing
February 2020

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes.

Front Genet 2019 13;10:1144. Epub 2019 Nov 13.

Bioinformatics Laboratory (LABINFO), National Laboratory for Scientific Computing (LNCC), Petrópolis, Brazil.

RASopathies are a group of rare genetic diseases caused by germline mutations in genes involved in the RAS-mitogen-activated protein kinase (RAS-MAPK) pathway. Whole-exome sequencing (WES) is a powerful approach for identifying new variants in coding and noncoding DNA sequences, including miRNAs. miRNAs are fine-tuning negative regulators of gene expression. Read More

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http://dx.doi.org/10.3389/fgene.2019.01144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863982PMC
November 2019

mTOR pathway in human cardiac hypertrophy caused by LEOPARD syndrome: a different role compared with animal models?

Orphanet J Rare Dis 2019 11 13;14(1):252. Epub 2019 Nov 13.

State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China.

Background: Animal studies suggested that blocking the activation of the mammalian target of rapamycin (mTOR) pathway might be effective to treat cardiac hypertrophy in LEOPARD syndrome (LS) caused by PTPN11 mutations.

Results: In the present study, mTOR pathway activity was examined in human myocardial samples from two patients with LS, four patients with hypertrophic cardiomyopathy (HCM), and four normal controls. The two patients with LS had p. Read More

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http://dx.doi.org/10.1186/s13023-019-1204-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854668PMC
November 2019

Shp2 in myocytes is essential for cardiovascular and neointima development.

J Mol Cell Cardiol 2019 12 18;137:71-81. Epub 2019 Oct 18.

Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:

Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Shp2, cause Noonan syndrome and LEOPARD syndrome, inherited multifaceted diseases including cardiac and vascular defects. However, the function of Shp2 in blood vessels, especially in vascular smooth muscle cells (VSMCs), remains largely unknown. We generated mice in which Shp2 was specifically deleted in VSMCs and embryonic cardiomyocytes using the SM22α-Cre transgenic mouse line. Read More

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http://dx.doi.org/10.1016/j.yjmcc.2019.09.014DOI Listing
December 2019
2 Reads

[Case report and diagnosis of Noonan syndrome with multiple lentigines with deafness as its main clinical feature].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2019 Sep;33(9):804-807

Noonan syndrome with multiple lentigines(NSML) is a disorder with syndromic hearing loss. Abnormalities of other systems in NSML have received increasing attention, but hearing loss is rarely concerned. And due to the incomplete phenotype, some patients with NSML maybe missed or maybe confused with other syndromic deafness such as Waardenburg syndrome. Read More

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http://dx.doi.org/10.13201/j.issn.1001-1781.2019.09.003DOI Listing
September 2019
1 Read

Giant coronary artery aneurysm in a patient with LEOPARD syndrome.

Eur Heart J Case Rep 2019 Sep;3(3)

Department of Cardiovascular Imaging, Hôpital Cardiologique du Haut Lévêque, CHU Bordeaux, Pessac, France.

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http://dx.doi.org/10.1093/ehjcr/ytz088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764546PMC
September 2019
1 Read

Pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: the multifaceted consequences of PTPN11 mutations.

Orphanet J Rare Dis 2019 07 5;14(1):163. Epub 2019 Jul 5.

Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital and Research Institute, Viale di San Paolo 15, 00146, Rome, Italy.

The concomitant occurrence of hypertrophic cardiomyopathy and congenital heart defect in patients with RASopathies has previously been reported as associated to a worse clinical outcome, particularly closed to cardiac surgery. Different mechanisms of disease have been demonstrated to be associated with the two classes of PTPN11 mutations underlying Noonan syndrome and Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome). Although differential diagnosis between these two syndromes could be difficult, particularly in the first age of life, we underline the relevance in discriminating these two disorders in terms of affected signaling pathway to allow an effective targeted pharmacological treatment. Read More

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http://dx.doi.org/10.1186/s13023-019-1151-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610955PMC
July 2019
3 Reads

Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation.

J Biomol Struct Dyn 2020 Jun 1;38(9):2509-2520. Epub 2019 Jul 1.

School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin, China.

Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome (LS), is an autosomal dominant inherited multisystemic disorder. Most patients involve mutation in SHP2 encoded by tyrosine-protein phosphatase non-receptor type 11 (PTPN11) gene. Studies have shown that NSML-associated Y279C mutation exhibited the reduced phosphatase activity, leading to loss-of-function (LOF) of SHP2. Read More

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http://dx.doi.org/10.1080/07391102.2019.1634641DOI Listing
June 2020
7 Reads

Noonan syndrome with multiple lentigines and prominent keratosis pilaris.

J Dtsch Dermatol Ges 2019 Jul 18;17(7):749-751. Epub 2019 Jun 18.

Department of Dermatology, Hospital Universitario de Cabueñes, Gijón, Spain.

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http://dx.doi.org/10.1111/ddg.13880DOI Listing
July 2019
6 Reads

Out-of-hospital cardiac arrest and survival in a patient with Noonan syndrome and multiple lentigines: a case report.

J Med Case Rep 2019 Jun 15;13(1):194. Epub 2019 Jun 15.

Department of Paediatric Cardiology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.

Background: A 9-year-old Arabic boy attending middle school presented with an out-of-hospital cardiac arrest due to ventricular fibrillation recorded by Holter electrocardiographic monitoring. He had a background history of Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome), a rare condition of autosomal dominant inheritance with approximately 200 cases reported worldwide.

Case Presentation: Apart from characteristic features, the boy was known to have asymmetric septal hypertrophy with a maximum wall thickness of 24 mm measured by cardiovascular magnetic resonance imaging. Read More

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http://dx.doi.org/10.1186/s13256-019-2096-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572739PMC
June 2019
18 Reads

RASopathy in Patients With Isolated Sagittal Synostosis.

Glob Pediatr Health 2019 12;6:2333794X19846774. Epub 2019 May 12.

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.

RASopathy is caused by dysfunction in the pathway, and include syndromes like Noonan syndrome (NS), NS with multiple lentigines (formerly known as Leopard syndrome), cardiofaciocutaneous (CFC), Legius syndrome, capillary malformation-arteriovenous malformation, neurofibromatosis type 1, and Costello syndrome. When counted together, RASopathies affect 1/1000 live births, and are characterized by cardiovascular manifestations, short stature, developmental delay, renal, urogenital, skin/skeletal abnormalities, and dysmorphic appearance. NS-one of the most common RASopathies-occurs in 1/1000 to 1/2500 live births. Read More

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http://dx.doi.org/10.1177/2333794X19846774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540476PMC
May 2019
11 Reads

Pathogenesis of Growth Failure in Rasopathies.

Pediatr Endocrinol Rev 2019 May;16(Suppl 2):447-458

Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London WC1N 3JH, Genetics and Genomic Medicine Programme, UCL GOS Institute of Child Health, E-mail:

The RASopathies are a group of developmental genetic syndromes that are caused by germline mutations in genes encoding proteins of the Ras-Mitogen-Activated Protein kinase (RAS-MAPK) pathway. RASopathies include Noonan Syndrome (NS), Neurofibromatosis Type 1 (NF1), Noonan syndrome with multiple lentigines (NSML/LEOPARD), Costello syndrome (CS), Cardio-facio-cutaneous syndrome (CFC), capillary malformation-arteriovenous malformation syndrome (CM-AVM) and Legius Syndrome. These syndromes have many overlapping features; however, the most persistent feature common to all is the postnatal growth failure. Read More

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http://dx.doi.org/10.17458/per.vol16.2019.ad.pathogenesisrasopathiesDOI Listing
May 2019
12 Reads

Have You Ever Seen a LEOPARD?

Authors:
Lucien Marchand

Am J Med 2019 09 30;132(9):e711. Epub 2019 Apr 30.

Department of Endocrinology and Diabetes, St. Joseph - St. Luc Hospital, Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2019.04.009DOI Listing
September 2019
5 Reads

Rasopathies case report: concurrence of two pathogenic variations de novo in NF1 and KRAS genes in a patient.

BMC Pediatr 2019 04 5;19(1):92. Epub 2019 Apr 5.

Neonatology Department, Miguel Servet Children's Hospital, Isabel la Católica Avenue 1-3, 50009, Zaragoza, Spain.

Background: Rasopathies are a group of genetic malformative syndromes including neurofibromatosis 1, Noonan, LEOPARD, Costello, cardio-facio-cutaneous, Legius, and capillary malformation-arteriovenous malformation syndromes.

Case Presentation: We present a female newborn that consulted at the emergency department with refusal to eat and sleepiness. A shortened femur, thickened nucal fold and suspect for agenesis of the corpus callosum were observed in prenatal ultrasound. Read More

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http://dx.doi.org/10.1186/s12887-019-1463-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449997PMC
April 2019
15 Reads
1.918 Impact Factor

Genetic landscape of RASopathies in Chinese: Three decades' experience in Hong Kong.

Am J Med Genet C Semin Med Genet 2019 06 21;181(2):208-217. Epub 2019 Mar 21.

Department of Health, Clinical Genetic Service, HKSAR, Hong Kong.

RASopathies are a group of genetic disorders due to dysregulation of the RAS-MAPK signaling pathway, which is important in regulating cell growth, proliferation, and differentiation. These include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), cardiofaciocutaneous (CFC) syndrome, and Costello syndrome (CS), clinical manifestations include growth retardation, developmental delay, cardiac defects, and specific dysmorphic features. There were abundant publications describing the genotype and phenotype from the Western populations. Read More

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http://dx.doi.org/10.1002/ajmg.c.31692DOI Listing
June 2019
9 Reads

Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene.

Stem Cell Res 2019 01 26;34:101374. Epub 2018 Dec 26.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD Syndrome, is a rare autosomal dominant disorder. Approximately 90% of NSML cases are caused by missense mutations in the PTPN11 gene which encodes the protein tyrosine phosphatase SHP2. A human induced pluripotent stem cell (iPSC) line was generated using peripheral blood mononuclear cells (PBMCs) from a patient with NSML that carries a gene mutation of p. Read More

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http://dx.doi.org/10.1016/j.scr.2018.101374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017387PMC
January 2019
7 Reads

Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines.

Int J Dermatol 2018 11 27;57(11):e140-e141. Epub 2018 Aug 27.

Department of Dermatology, University of Health Sciences, Ankara Numune Training and Research Hospital, Ankara, Turkey.

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http://doi.wiley.com/10.1111/ijd.14209
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http://dx.doi.org/10.1111/ijd.14209DOI Listing
November 2018
14 Reads

Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients.

Am J Med Genet A 2018 08 28;176(8):1711-1722. Epub 2018 Jul 28.

Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts.

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Read More

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http://dx.doi.org/10.1002/ajmg.a.38854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107379PMC
August 2018
38 Reads

Pregnancy-induced hypertension-related chorioretinitis resembling uveal effusion syndrome: A case report.

Medicine (Baltimore) 2018 Jul;97(30):e11572

Department of Ophthalmology, National Defense Medical College, Saitama, Japan.

Rationale: Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal mortality. Hypertensive choroidopathy is a preliminary sign of vasogenic edema in the choroid, and is associated with PIH. Here, we report a post-natal case of PIH-related chorioretinitis with bilateral severe serous retinal detachment (SRD) resembling uveal effusion syndrome. Read More

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http://dx.doi.org/10.1097/MD.0000000000011572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078765PMC
July 2018
4 Reads

Giraffe or leopard spot chorioretinopathy as an outstanding finding: case report and literature review.

Int Ophthalmol 2019 Jun 8;39(6):1405-1412. Epub 2018 Jun 8.

Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, No. 23, Paidarfard St., Pasdaran Ave., Tehran, 16666, Iran.

Purpose: Presentation of two typical cases with characteristic leopard retinopathy secondary to bilateral diffuse uveal melanocytic proliferation (BDUMP) and idiopathic uveal effusion syndrome (IUES) and brief review of the literature about leopard spot retinopathy.

Case Report: A 43-year-old women, who was a known case of ovarian carcinoma, referred with gradual bilateral visual loss. In ophthalmic examination, subretinal fluid, multiple patchy subretinal hyperpigmented lesions and leopard spot chorioretinopathy were evident in her both eyes. Read More

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http://link.springer.com/10.1007/s10792-018-0948-5
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http://dx.doi.org/10.1007/s10792-018-0948-5DOI Listing
June 2019
59 Reads

The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway.

Endocr Rev 2018 10;39(5):676-700

INSERM UMR 1048, Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France.

Noonan syndrome [NS; Mendelian Inheritance in Men (MIM) #163950] and related syndromes [Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome; MIM #151100), Noonan-like syndrome with loose anagen hair (MIM #607721), Costello syndrome (MIM #218040), cardio-facio-cutaneous syndrome (MIM #115150), type I neurofibromatosis (MIM #162200), and Legius syndrome (MIM #611431)] are a group of related genetic disorders associated with distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. NS was clinically described more than 50 years ago, and disease genes have been identified throughout the last 3 decades, providing a molecular basis to better understand their physiopathology and identify targets for therapeutic strategies. Most of these genes encode proteins belonging to or regulating the so-called RAS/MAPK signaling pathway, so these syndromes have been gathered under the name RASopathies. Read More

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http://dx.doi.org/10.1210/er.2017-00232DOI Listing
October 2018
54 Reads

Generalised lentiginosis and café noir spots leading to a diagnosis of LEOPARD syndrome.

Postgrad Med J 2018 Oct 11;94(1116):605. Epub 2018 Jun 11.

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://pmj.bmj.com/lookup/doi/10.1136/postgradmedj-2018-1358
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http://dx.doi.org/10.1136/postgradmedj-2018-135843DOI Listing
October 2018
13 Reads

RAS signalling in energy metabolism and rare human diseases.

Biochim Biophys Acta Bioenerg 2018 09 8;1859(9):845-867. Epub 2018 May 8.

Bordeaux University, 33000 Bordeaux, France; INSERM U1211, 33000 Bordeaux, France; CELLOMET, CGFB-146 Rue Léo Saignat, Bordeaux, France. Electronic address:

The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Read More

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http://dx.doi.org/10.1016/j.bbabio.2018.05.003DOI Listing
September 2018
7 Reads

Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy.

Acta Clin Belg 2019 Apr 2;74(2):82-85. Epub 2018 May 2.

e Biomedical Center Martin, Jessenius Faculty of Medicine in Martin , Comenius University in Bratislava , Martin , Slovakia.

Introduction LEOPARD syndrome is a rare genetic disorder characterised by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth and sensorineural deafness. Clinical manifestations are often mild, which may result in difficult and late diagnosis. Cardiac involvement may have a significant impact on the prognosis, however, appearance of severe abnormalities such as hypertrophic cardiomyopathy usually precedes the occurrence of multiple lentigines and may be asymptomatic. Read More

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http://dx.doi.org/10.1080/17843286.2018.1467531DOI Listing
April 2019
6 Reads

A Rare Case of Left Ventricular Noncompaction in LEOPARD Syndrome.

J Cardiovasc Ultrasound 2018 Mar 28;26(1):43-44. Epub 2018 Mar 28.

Department of Internal Medicine, Gyeonsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.

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http://dx.doi.org/10.4250/jcu.2018.26.1.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881084PMC
March 2018
11 Reads

Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy.

Circ Heart Fail 2018 04;11(4):e004660

Department of Pediatrics (Y.N., R.I., H.T., S.K., K.S., H.A., T.S., Y.H., A.O.), Department of Pathology (K.I., M.H.), Department of Cardiovascular Medicine (N.T.), and Department of Developmental Medical Sciences (M.S.), Graduate School of Medicine, The University of Tokyo, Japan.

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004660DOI Listing
April 2018
16 Reads

[LEOPARD syndrome: A variant of Noonan syndrome with lentigines].

An Pediatr (Barc) 2018 Jul 20;89(1):66-67. Epub 2018 Mar 20.

Servicio de Neuropediatría, Hospital Regional Universitario, Málaga, España.

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http://dx.doi.org/10.1016/j.anpedi.2018.01.017DOI Listing
July 2018
8 Reads

Gain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.

Sci Signal 2018 03 20;11(522). Epub 2018 Mar 20.

Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA.

Catalytically activating mutations in , which encodes the protein tyrosine phosphatase SHP2, cause 50% of Noonan syndrome (NS) cases, whereas inactivating mutations in are responsible for nearly all cases of the similar, but distinct, developmental disorder Noonan syndrome with multiple lentigines (NSML; formerly called LEOPARD syndrome). However, both types of disease mutations are gain-of-function mutations because they cause SHP2 to constitutively adopt an open conformation. We found that the catalytic activity of SHP2 was required for the pathogenic effects of gain-of-function, disease-associated mutations on the development of hydrocephalus in the mouse. Read More

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http://dx.doi.org/10.1126/scisignal.aao1591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915342PMC
March 2018
7 Reads

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

Heart Fail Clin 2018 Apr;14(2):225-235

Pediatric Cardiology, Department of Pediatrics, Sapienza University, Viale Regina Elena 324, Rome 00161, Italy.

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. Read More

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http://dx.doi.org/10.1016/j.hfc.2017.12.005DOI Listing
April 2018
31 Reads

Patient with confirmed LEOPARD syndrome developing multiple melanoma.

Dermatol Pract Concept 2018 Jan 31;8(1):59-62. Epub 2018 Jan 31.

Department of Dermatology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome, lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as Noonan syndrome with multiple lentigines (NSML), inside the RASopathies. Historically, the acronym LEOPARD refers to the presence of distinctive clinical features such as: lentigines (L), electrocardiographic/conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A), retardation of growth (R), and sensorineural deafness (D). This condition is identified in 85% of patients with phenotype hallmarks caused by presence a germline point mutation in PTPN11 gene. Read More

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http://dx.doi.org/10.5826/dpc.0801a14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808376PMC
January 2018
10 Reads

Noonan syndrome with multiple lentigines and associated craniosynostosis.

Clin Exp Dermatol 2018 Apr 22;43(3):357-359. Epub 2018 Jan 22.

Department of Dermatology, Watford General Hospital, Hertfordshire Hospitals NHS Trust, Watford, Hertfordshire, UK.

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http://dx.doi.org/10.1111/ced.13329DOI Listing
April 2018
10 Reads

Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.

BMC Med Genomics 2017 10 30;10(1):62. Epub 2017 Oct 30.

Department of Pediatric Endocrinology/Genetics, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES). Read More

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http://dx.doi.org/10.1186/s12920-017-0298-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663114PMC
October 2017
25 Reads

Activation of Autophagy Ameliorates Cardiomyopathy in -Targeted Knockin Mice.

Circ Heart Fail 2017 Oct;10(10)

From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Germany (S.R.S., A.T.L.Z., B.G., S.R.-D., M.P., E.K., S.S., L.C.); DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (S.R.S., A.T.L.Z., B.G., S.R.-D., M.P., E.K., S.S., L.C.); Department of Pediatrics, The Heart Institute, The Cincinnati Children's Hospital Medical Center, OH (S.R.S., H.O., Q.M., J.R.); Radcliffe Department of Medicine, University of Oxford, United Kingdom (C.R.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (J.v.d.V.); and ICIN-Netherlands Heart Institute, Utrecht (J.v.d.V.).

Background: Alterations in 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 cases. , encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene.

Methods And Results: We evaluated autophagy in patients with HCM carrying mutations and in a -targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice. Read More

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679453PMC
October 2017
86 Reads

Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines.

J Mol Cell Cardiol 2017 11 11;112:83-90. Epub 2017 Sep 11.

Dalton Cardiovascular Research Center, Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, 134 Research Park Dr, Columbia, MO 65211, United States. Electronic address:

Noonan Syndrome with Multiple Lentigines (NSML) is associated with congenital heart disease in form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Genetically, NSML is primarily caused by mutations in the non-receptor protein tyrosine phosphatase SHP2. Importantly, certain SHP2 mutations such as Q510E can cause a particularly severe form of HCM with heart failure in infancy. Read More

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http://dx.doi.org/10.1016/j.yjmcc.2017.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647241PMC
November 2017
58 Reads

Clinical, pathological and dermoscopic characteristics of cutaneous lesions in LEOPARD syndrome.

J Eur Acad Dermatol Venereol 2018 Mar 14;32(3):e100-e101. Epub 2017 Sep 14.

Dermatology Department, Hospital Sant Pau i Santa Tecla, Tarragona, Spain.

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http://dx.doi.org/10.1111/jdv.14573DOI Listing
March 2018
9 Reads

Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor.

J Dermatol 2017 Nov 5;44(11):e280-e281. Epub 2017 Jul 5.

Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1111/1346-8138.13960DOI Listing
November 2017
2 Reads

A review of craniofacial and dental findings of the RASopathies.

Orthod Craniofac Res 2017 Jun;20 Suppl 1:32-38

Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA.

Objectives: The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML or LEOPARD syndrome), neurofibromatosis type 1 (NF1), Costello syndrome (CS), cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type 1-like syndrome (NFLS or Legius syndrome) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). These disorders affect multiple systems, including the craniofacial complex. Read More

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http://dx.doi.org/10.1111/ocr.12144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942188PMC
June 2017
36 Reads

[Overlap syndrome. LEOPARD and neurofibromatosis. A case report].

Rev Med Inst Mex Seguro Soc 2017 Jul-Aug;55(4):540-543

Servicio de Terapia Intensiva, Hospital General de Zona 30 "Iztacalco", Instituto Mexicano del Seguro Social, Ciudad de México, México.

We expose a clinical case of a 43-year-old patient who was attended at the Dermatology service in a general hospital of the Instituto Mexicano del Seguro Social, with a disseminated pattern of lentigines, psychomotor retardation and electrocardiographic abnormalities. Afterwards, we made an analysis of the literature. Read More

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April 2018
28 Reads

In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy.

PLoS One 2017 5;12(6):e0178905. Epub 2017 Jun 5.

Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.

Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459472PMC
September 2017
85 Reads

[Update on the treatment of RASopathies].

Rev Neurol 2017 May;64(s03):S13-S17

Hospital Infantil Universitario Nino Jesus, 28009 Madrid, Espana.

Introduction: The term 'RASopathies' covers a series of diseases that present mutations in the genes that code for the proteins of the RAS/MAPK pathway. These diseases include neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome. Involvement of the RAS/MAPK pathway not only increases predisposition to develop tumours, but also determines the presence of phenotypic anomalies and alterations in learning processes. Read More

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May 2017
56 Reads

Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11.

Int J Pediatr Otorhinolaryngol 2017 Jun 17;97:228-234. Epub 2017 Apr 17.

Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. Read More

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http://dx.doi.org/10.1016/j.ijporl.2017.04.024DOI Listing
June 2017
25 Reads

Do you know this syndrome? Leopard syndrome.

An Bras Dermatol 2017 Jan-Feb;92(1):127-129

Odontology Department of the Pontifícia Universidade Católica de Minas Gerais (PUC Minas) - Belo Horizonte (MG), Brazil.

Hypertrophic cardiomyopathy is known as Leopard syndrome, which is a mnemonic rule for multiple lentigines (L), electrocardiographic conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), abnormalities of genitalia (A), retardation of growth (R), and deafness (D). We report the case of a 12-year-old patient with some of the abovementioned characteristics: hypertelorism, macroglossia, lentigines, hypospadias, cryptorchidism, subaortic stenosis, growth retardation, and hearing impairment. Due to this set of symptoms, we diagnosed Leopard syndrome. Read More

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http://dx.doi.org/10.1590/abd1806-4841.20174505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312195PMC
October 2017
18 Reads