467 results match your criteria LEOPARD Syndrome

Central Serous Chorioretinopathy mimicking Idiopathic Uveal Effusion Syndrome.

Retin Cases Brief Rep 2021 Jun 1. Epub 2021 Jun 1.

Université de Paris, Ophthalmology Department, APHP, Hôpital Lariboisière, F-75010, Paris, France Centre d'Imagerie et Laser, F-75015, Paris, France.

Purpose: To describe central serous chorioretinopathy (CSCR) cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases.

Methods: Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging and biometry of four eyes of three patients were assessed. A literature review was conducted. Read More

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Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9.

Science 2021 05 27;372(6545):941-948. Epub 2021 Apr 27.

Helmholtz Institute for RNA-based Infection Research (HIRI)/Helmholtz-Centre for Infection Research (HZI), 97080 Würzburg, Germany.

CRISPR-Cas systems recognize foreign genetic material using CRISPR RNAs (crRNAs). In type II systems, a trans-activating crRNA (tracrRNA) hybridizes to crRNAs to drive their processing and utilization by Cas9. While analyzing Cas9-RNA complexes from , we discovered tracrRNA hybridizing to cellular RNAs, leading to formation of "noncanonical" crRNAs capable of guiding DNA targeting by Cas9. Read More

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LEPOARD syndrome: A report of a case with a novel PTPN11 mutation.

JAAD Case Rep 2021 May 20;11:57-59. Epub 2021 Mar 20.

Department of Dermatology, Ha'emek Medical Center, Afula, Israel.

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A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors.

Acta Pharm Sin B 2021 Mar 31;11(3):750-762. Epub 2020 Oct 31.

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Read More

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Noonan Syndrome with Multiple Lentigines and Mutation: A Case with Intracerebral Hemorrhage.

Mol Syndromol 2021 Mar 27;12(1):57-63. Epub 2021 Jan 27.

Research Group in Neurosciences (NEUROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.

Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome, is a rare autosomal dominant disorder with an unknown prevalence. Characteristics of this disease include cutaneous, neurologic, and cardiologic abnormalities. In this case report, we present a 12-year-old girl who was admitted to the emergency department for acute-onset left weakness, unsteady gait, nausea, and vomiting. Read More

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Multimodal imaging to aid in diagnosis of uveal effusion syndrome type 3.

BMJ Case Rep 2021 Mar 2;14(3). Epub 2021 Mar 2.

Advanced eye centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India

A 47-year-old man presented to our retina clinic with gradual onset diminution of vision in his right eye for the last 3 months. Anterior segment evaluation was normal in both eyes. Fundus evaluation showed the presence of leopard spot appearance in the right eye with inferior exudative retinal detachment. Read More

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Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report.

BMC Med Genomics 2021 01 21;14(1):25. Epub 2021 Jan 21.

Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot-Marie-Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients.

Case Presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months.

Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene. Read More

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January 2021

Compound heterozygosity for PTPN11 variants in a subject with Noonan syndrome provides insights into the mechanism of SHP2-related disorders.

Clin Genet 2021 Mar 4;99(3):457-461. Epub 2021 Jan 4.

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

The RASopathies are a family of clinically related disorders caused by mutations affecting genes participating in the RAS-MAPK signaling cascade. Among them, Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are allelic conditions principally associated with dominant mutations in PTPN11, which encodes the nonreceptor SH2 domain-containing protein tyrosine phosphatase SHP2. Individual PTPN11 mutations are specific to each syndrome and have opposite consequences on catalysis, but all favor SHP2's interaction with signaling partners. Read More

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Allosteric inhibitors of SHP2: an updated patent review (2015-2020).

Curr Med Chem 2020 Sep 28. Epub 2020 Sep 28.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070. China.

Srchomology-2-domain-containing PTP 2 (SHP2) is a nonreceptor phosphatase encoded by the PTPN11 gene. Over expression of SHP2 is associated with various human diseases, such as Noonan syndrome, LEOPARD syndrome, and cancers. To overcome the shortcomings of existing orthosteric inhibitors, novel inhibitors targeting the allosteric site of SHP2 with high selectivity and low toxicity are under development. Read More

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September 2020

Introduction to phacomatoses (neurocutaneous disorders) in childhood.

Childs Nerv Syst 2020 10 17;36(10):2229-2268. Epub 2020 Sep 17.

Pediatric Neurosurgery, International Neuroscience Institute [INI], Hanover, Germany.

The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word "ϕαχοσ" = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. Read More

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October 2020

Phosphatase-independent functions of SHP2 and its regulation by small molecule compounds.

Wenjie Guo Qiang Xu

J Pharmacol Sci 2020 Nov 3;144(3):139-146. Epub 2020 Aug 3.

State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, 210093, China. Electronic address:

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene in human. Clinically, SHP2 has been identified as a causal factor of several diseases, such as Noonan syndrome, LEOPARD syndrome as well as myeloid malignancies. Interestingly, both loss-of-function and gain-of-function mutations occur in the PTPN11 gene. Read More

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November 2020

Familial LEOPARD Syndrome With Hypertrophic Cardiomyopathy.

Am J Cardiol 2020 11 28;135:168-173. Epub 2020 Aug 28.

Aurora Cardiovascular and Thoracic Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, Wisconsin. Electronic address:

Multiple lentigines syndrome is an autosomal dominant inherited condition with variable expressivity that is also known as LEOPARD syndrome. LEOPARD stands for lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, abnormalities of genitalia, retardation of growth, and deafness. LEOPARD syndrome most frequently develops secondary to a missense mutation of protein-tyrosine phosphatase nonreceptor type 11 gene, which encodes tyrosine phosphatase. Read More

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November 2020

LEOPARD Syndrome with Gene Mutation in Three Family Members Presenting with Different Phenotypes.

J Pediatr Genet 2020 Dec 15;9(4):246-251. Epub 2019 Nov 15.

Department of Dermatology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

LEOPARD syndrome (LS) is a rare autosomal dominant disorder that is characterized by multiple lentigines and various congenital anomalies. The clinical diagnosis of LS requires molecular confirmation. The most frequently reported mutations in LS patients are in the protein tyrosine phosphatase nonreceptor type 11 gene, . Read More

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December 2020

Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines.

JCI Insight 2020 08 6;5(15). Epub 2020 Aug 6.

Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.

Noonan syndrome with multiple lentigines (NSML) is a rare autosomal dominant disorder that presents with cardio-cutaneous-craniofacial defects. Hypertrophic cardiomyopathy (HCM) represents the major life-threatening presentation in NSML. Mutations in the PTPN11 gene that encodes for the protein tyrosine phosphatase (PTP), SHP2, represents the predominant cause of HCM in NSML. Read More

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

Actas Dermosifiliogr (Engl Ed) 2020 Sep 9;111(7):619-621. Epub 2020 Jun 9.

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

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September 2020

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

An Pediatr (Engl Ed) 2020 Jul 31;93(1):61.e1-61.e14. 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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[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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P-Related Protein Accelerates Human Mesenchymal Stromal Cell Migration by Modulating VLA-5 Interactions with Fibronectin.

Cells 2020 04 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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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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Images of the month 2: A leopard never changes its spots.

Clin Med (Lond) 2020 03;20(2):231-232

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

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Therapeutic potential of targeting SHP2 in human developmental disorders and cancers.

Eur J Med Chem 2020 Mar 6;190:112117. Epub 2020 Feb 6.

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, regulates cell proliferation, differentiation, apoptosis and survival via releasing intramolecular autoinhibition and modulating various signaling pathways, such as mitogen-activated protein kinase (MAPK) pathway. Mutations and aberrant expression of SHP2 are implicated in human developmental disorders, leukemias and several solid tumors. As an oncoprotein in some cancers, SHP2 represents a rational target for inhibitors to interfere. Read More

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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 2021 Mar 25;39(4):1174-1188. 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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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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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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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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November 2019

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Prenat Diagn 2020 01 27;40(2):197-205. Epub 2019 Nov 27.

Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Objectives: To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities.

Methods: This is a national study including 1901 pregnancies with NT≥95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Read More

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January 2020

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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December 2019

[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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September 2019

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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September 2019

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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