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Veterinary World Oct 2021The recent coronavirus disease (COVID-19) outbreak is one of its kind in the history of public health that has created a major global threat. The causative agent, severe... (Review)
Review
The recent coronavirus disease (COVID-19) outbreak is one of its kind in the history of public health that has created a major global threat. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a zoonotic source and hence, reverse zoonosis (disease transmission from humans to animals) increases the risk and rate of SARS-CoV-2 infection. Serological and molecular analyses and experimental infection studies have identified SARS-CoV-2 infection in several animal species in various countries. Different domestic and wild animals, including cats, dogs, tigers, lions, puma, snow leopard, minks, and pet ferrets, are infected naturally with SARS-CoV-2, mostly through suspected human to animal transmission. In addition, in vivo experimental inoculation studies have reported the susceptibility of cats, ferrets, hamsters, Egyptian fruit bats, and non-human primates to the virus. These experimentally infected species are found to be capable of virus transmission to co-housed animals of the same species. However, SARS-CoV-2 showed poor replication in livestock species such as pigs, chickens, and ducks with no detection of viral RNA after the animals were deliberately inoculated with the virus or exposed to the infected animals. As the pets/companion animals are more susceptible to COVID-19, the infection in animals needs an in-depth and careful study to avoid any future transmissions. The one health approach is the best inter-disciplinary method to understand the consequences of viral spread and prevention in novel host populations for the betterment of public health. Further in this review, we will explain in detail the different natural and experimentally induced cases of human to animal SARS-CoV-2 infection.
PubMed: 34903944
DOI: 10.14202/vetworld.2021.2817-2826 -
Genetics in Medicine : Official Journal... Jun 2017RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms.... (Review)
Review
INTRODUCTION
RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies.
MATERIALS AND METHODS
The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies.
RESULTS
Twenty-four patients had pathogenic variants on the RASopathy panel, for a diagnostic yield of 19%. Reported features of pulmonic stenosis and ptosis were significantly correlated with a positive test result; no reported features were significantly correlated with a negative test result. We identified 27 different alternative diagnoses for patients originally suspected of having RASopathies.
DISCUSSION
This study provides information that can assist in guiding differential diagnosis and genetic testing for patients suspected of having a RASopathy disorder.Genet Med advance online publication 20 October 2016.
Topics: Costello Syndrome; High-Throughput Nucleotide Sequencing; Humans; LEOPARD Syndrome; MAP Kinase Signaling System; Noonan Syndrome; Phenotype; Retrospective Studies; ras Proteins
PubMed: 27763634
DOI: 10.1038/gim.2016.169 -
LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.Proceedings of the National Academy of... Oct 2014LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of...
LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders.
Topics: Adipocytes; Adipose Tissue; Adiposity; Animals; Body Composition; Cell Differentiation; Diet; Disease Models, Animal; Energy Metabolism; Insulin; LEOPARD Syndrome; Lentivirus; Lipolysis; MAP Kinase Kinase Kinase 1; Male; Mice; Mice, Transgenic; Mutation; Obesity; Phenotype; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Recombination, Genetic; Thinness
PubMed: 25288766
DOI: 10.1073/pnas.1406107111 -
Acta Dermato-venereologica Jan 2024
Topics: Humans; LEOPARD Syndrome; Melanoma; Mutation; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 38189222
DOI: 10.2340/actadv.v104.14720 -
Indian Journal of Dermatology,... 2016
PubMed: 26728819
DOI: 10.4103/0378-6323.171642 -
Molecular Syndromology Mar 2021Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome, is a rare autosomal dominant disorder with an unknown prevalence. Characteristics...
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. Her physical exam notably showed left side upper motor neuron signs and dysmetria. CT scan revealed an acute hemorrhage of the right thalamus. Physical exam exhibited several craniofacial dysmorphisms and lentigines. The genetic test revealed a heterozygous missense mutation in the protein tyrosine phosphatase non-receptor type 11 () gene and a variant of unknown significance of the gene. To the best of our knowledge, this is the first case of a patient with NSML presenting an intracerebral hemorrhage.
PubMed: 33776629
DOI: 10.1159/000512374 -
Frontiers in Pediatrics 2022The gene, located at 12q24. 13, encodes protein tyrosine phosphatase 2C. Mutations in the gene can lead to various phenotypes, including Noonan syndrome and LEOPARD...
BACKGROUND
The gene, located at 12q24. 13, encodes protein tyrosine phosphatase 2C. Mutations in the gene can lead to various phenotypes, including Noonan syndrome and LEOPARD syndrome. The gene is located at 4q26 and encodes a component of the COPII complex, and is closely related to endoplasmic reticulum protein transport. Mutations in can lead to Cole-Carpenter syndrome-2. To date, dual mutations in these two genes have not been reported in the literature.
METHODS
We report a patient with short stature and osteogenesis imperfecta as the primary clinical manifestation. Other clinical features were peculiar facial features, deafness, and a history of recurrent fractures. Whole exome sequencing was performed on this patient.
RESULTS
After whole-exome sequencing, three mutations in two genes were identified that induced protein alterations associated with the patient's phenotype. One was a de novo variant c.1403C>T (p.Thr468Met) on exon 12 of the gene, and the other was a compound heterozygous mutation in the gene, a novel variant c.2609_2610delGA (p.Arg870Thrfs10) on exon 20 and a reported variant c.938G>A (p.Arg313His) on exon 8.
CONCLUSIONS
Concurrent mutations in and induced a phenotype that was significantly different from individual mutations in either or gene. Personalized genetic analysis and interpretation could help us understand the patient's etiology and hence develop treatments and improve the prognosis of these patients.
PubMed: 36186652
DOI: 10.3389/fped.2022.973920 -
BMC Neurology Apr 2015LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome,...
BACKGROUND
LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair and Legius syndrome. These conditions are caused by mutations in genes encoding proteins involved in the RAS-MAPK cellular pathway. Clinical heterogeneity and phenotype overlaps across those different syndromes is already recognized.
CASE PRESENTATION
We hereby report a heterozygous de novo mutation in the PTPN11 gene (c.1403C > T) manifesting with a clinical picture of LS during childhood, and later development of neuropathic pain with hypertrophic plexi, which are typically observed in NF1 but have not been reported in LS.
CONCLUSION
LS caused by PTPN11 mutations may be associated with hypertrophic roots and plexi. Consequently, clinicians should be aware of the possible development of neuropathic pain and consider specific diagnostic work-up and management.
Topics: Adult; Female; Humans; LEOPARD Syndrome; Mutation; Neuralgia; Peripheral Nervous System Diseases; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 25884655
DOI: 10.1186/s12883-015-0310-8 -
Genes Mar 2024Noonan syndrome is a group of diseases with a similar clinical picture, consisting of 16 diseases caused by mutations in 15 genes. According to the literature,...
Noonan syndrome is a group of diseases with a similar clinical picture, consisting of 16 diseases caused by mutations in 15 genes. According to the literature, approximately half of all cases are attributed to Noonan syndrome type 1, NSML, caused by mutations in the gene. We analyzed 456 unrelated probands using a gene panel NGS, and in 206 cases, the cause of the disease was identified. Approximately half of the cases (107) were caused by variants in the gene, including three previously undescribed variants, one of which was classified as VOUS, and the other two as LP causative complex alleles. Frequent variants of the gene characteristics for Russian patients were identified, accounting for more than 38% (c.922A>G p.Asn308Asp, c.417G>C p.Glu139Asp, c.1403C>T p.Thr468Met) of all cases with mutations in the gene. A comparative characterization of frequent variants of the gene in different populations is shown. The most common features of Noonan syndrome in the studied sample were facial dysmorphisms and cardiovascular system abnormalities. A lower representation of patients with growth delay was observed compared to previously described samples.
Topics: Humans; Noonan Syndrome; Mutation; Alleles; Russia; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 38540404
DOI: 10.3390/genes15030345 -
PloS One 2014Noonan syndrome (NS) and LEOPARD syndrome (LS) cause congenital afflictions such as short stature, hypertelorism and heart defects. More than 50% of NS and almost all of...
Noonan syndrome (NS) and LEOPARD syndrome (LS) cause congenital afflictions such as short stature, hypertelorism and heart defects. More than 50% of NS and almost all of LS cases are caused by activating and inactivating mutations of the phosphatase Shp2, respectively. How these biochemically opposing mutations lead to similar clinical outcomes is not clear. Using zebrafish models of NS and LS and mass spectrometry-based phosphotyrosine proteomics, we identified a down-regulated peptide of Fer kinase in both NS and LS. Further investigation showed a role for Fer during development, where morpholino-based knockdown caused craniofacial defects, heart edema and short stature. During gastrulation, loss of Fer caused convergence and extension defects without affecting cell fate. Moreover, Fer knockdown cooperated with NS and LS, but not wild type Shp2 to induce developmental defects, suggesting a role for Fer in the pathogenesis of both NS and LS.
Topics: Animals; Gene Knockdown Techniques; LEOPARD Syndrome; Mutation; Noonan Syndrome; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein-Tyrosine Kinases; Proteomics; Zebrafish; Zebrafish Proteins
PubMed: 25184253
DOI: 10.1371/journal.pone.0106682