Noonan syndrome with RAF1 gene mutations in a newborn with cerebral haemorrhage

Lan, Junwei; Zeng, Tianbao; Liu, Sheng; Lan, Ju-Hong; Qian, Lijun

doi:10.1186/s40001-022-00772-2

Cited by 4 publications

(7 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to be aware of potential genetic factors and syndromes contributing to an increased risk of PFHs in neonates, such as CCD, 6 hemophilia A, 7 COL4A1 mutation, 8 RASopathies such as NS, 9 and HHT. 10 11…”

Section: Discussionmentioning

confidence: 99%

“…Given that RAF1 plays a crucial role in vascular matrix production, 64 they hypothesized that the mutation in RAF1 gene can lead to cerebral vascular malformation and the consequent cerebral hemorrhage. 9 While no causal link has been established, clinicians should be aware of the potential link between NS and PFH.…”

Section: Discussionmentioning

confidence: 99%

“…Lan et al also described a case of NS with cerebral hemorrhage. 9 Razzaque et al 63 demonstrated that "RASopathy" conditions are caused by gain-of-function mutations in genes implicated in the RAS-MAPK signaling pathway. Seven genes are known to cause NS, with PTPN11 accounting for approximately 50% of cases.…”

Section: Comprehensive Clinical and Neuroimaging Review Of Posterior ...mentioning

confidence: 99%

“…1 Risk factors for PFH include emergent cesarean section, 2 cardiovascular conditions, most common being patent ductus arteriosus, 2 sepsis, 3 and acidosis (lower 5-day minimum pH), 2 devices-assisted deliveries such as vacuum 4 and forceps 5 in emergency situations, multiple gestations, 3 lack of antenatal steroids, 3 fetal heart rate abnormalities, 3 use of volume expanders and cardiotrophin, 3 and extracorporeal membrane oxygenation (ECMO) use. 6 Genetic causes include cleidocranial dysostosis (CCD), 6 hemophilia A, 7 COL4A1 mutation, 8 RASopathy such as Noonan syndrome (NS), 9 and hereditary hemorrhagic telangiectasia (HHT). 10 11 Cranial ultrasound, encephalogram, head magnetic resonance imaging (MRI), and head computed tomography (CT) are important tools in diagnosing PFH, with head MRI being the gold standard.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Hsu,

Zhu,

Islam

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

Posterior fossa hemorrhage (PFH) is a highly morbid condition in preterm and term infants. In this article, we aim to first describe a case of PFH, and using this example, provide a comprehensive narrative review of the pathophysiology, risk factors, diagnosis, and management of PFH. Management may differ depending on the etiology and based on careful consideration of the risks and benefits of surgical versus conservative management.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Comprehensive Clinical and Neuroimaging Review Of Posterior ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Hsu,

Zhu,

Islam

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

show abstract

“…Other experiments reported the activation of Ras-RAF-MEK-ERk stimulating the replication of Hepatitis C virus by downregulating the interferon-JAK-STAT pathway [ 70 ], while the Hepatitis B virus can regulate the RAF1 expression in HepG2.2.15 cell inducing hepatocellular carcinoma [ 67 ]. Moreover, the recent study indicated that multiple gene mutations of the Ras-MAPK signaling pathway can cause the Noonan syndrome (NS) which results in multiorgan disorder including bleeding and coagulation [ 72 ]. It is most commonly caused by a deficiency of factor XI followed by a reduced activity of factors VIII, XII, von Willebrand factor (vWF), thrombocytopenia, and platelet functional defect [ 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Serum proteomic profile of wild stump-tailed macaques (Macaca arctoides) infected with malaria parasites in Thailand

Ruengket,

Roytrakul,

Tongthainan

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

The number of patients infected with simian malaria is gradually increasing in many countries of Southeast Asia and South America. The most important risk factor for a zoonotic spillover event of malarial infection is mostly influenced by the interaction between humans, monkeys, and vectors. In this study, we determine the protein expression profile of a wild stump-tailed macaque (Macaca arctoides) from a total of 32 blood samples collected from Prachuap Kiri Khan Province, Thailand. The malarial parasite was analyzed using nested polymerase chain reaction (PCR) assays by dividing the samples into three groups: non-infected, mono-infected, and multiple-infected. The identification and differential proteomic expression profiles were determined using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and bioinformatics tools. A total of 9,532 proteins (total proteins) were identified with the filter-based selection methods analysis, and a subset of 440 proteins were found to be different between each group. Within these proteins, the GhostKOALA functional enrichment analysis indicated that 142 important proteins were associated with either of the organismal system (28.87%), genetic information processing (23.24%), environmental information processing (16.20%), metabolism (13.38%), cellular processes (11.97%), or causing human disease (6.34%). Additionally, using interaction network analysis, nine potential reporter proteins were identified. Here, we report the first study on the protein profiles differentially expressed in the serum of wild stump-tailed macaques between non, mono, and multiple malarial infected living in a natural transmission environment. Our findings demonstrate that differentially expressed proteins implicated in host defense through lipid metabolism, involved with TGF pathway were suppressed, while those with the apoptosis pathway, such as cytokines and proinflammation signals were increased. Including the parasite’s response via induced hemolysis and disruption of myeloid cells. A greater understanding of the fundamental processes involved in a malarial infection and host response can be crucial for developing diagnostic tools, medication development, and therapies to improve the health of those affected by the disease.

show abstract

RASopathies and cardiac manifestations

Hilal

Chen

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer and RASopathies, mutations in the genes that regulate RAS signaling or the RAS itself permanently activate the RAS protein. The structural basis of this switch is well understood; however, the exact mechanisms by which RAS proteins are regulated are less clear. RAS/MAPK syndromes are multisystem developmental disorders caused by germline mutations in genes associated with the RAS/mitogen-activated protein kinase pathway, impacting 1 in 1,000–2,500 children. These include a variety of disorders such as Noonan syndrome (NS) and NS-related disorders (NSRD), such as cardio facio cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML, also known as LEOPARD syndrome). A frequent manifestation of cardiomyopathy (CM) and hypertrophic cardiomyopathy associated with RASopathies suggest that RASopathies could be a potential causative factor for CM. However, the current supporting evidence is sporadic and unclear. RASopathy-patients also display a broad spectrum of congenital heart disease (CHD). More than 15 genes encode components of the RAS/MAPK signaling pathway that are essential for the cell cycle and play regulatory roles in proliferation, differentiation, growth, and metabolism. These genes are linked to the molecular genetic pathogenesis of these syndromes. However, genetic heterogeneity for a given syndrome on the one hand and alleles for multiple syndromes on the other make classification difficult in diagnosing RAS/MAPK-related diseases. Although there is some genetic homogeneity in most RASopathies, several RASopathies are allelic diseases. This allelism points to the role of critical signaling nodes and sheds light on the overlap between these related syndromes. Even though considerable progress has been made in understanding the pathophysiology of RASopathy with the identification of causal mutations and the functional analysis of their pathophysiological consequences, there are still unidentified causal genes for many patients diagnosed with RASopathies.

show abstract

Noonan syndrome with RAF1 gene mutations in a newborn with cerebral haemorrhage

Cited by 4 publications

References 16 publications

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Serum proteomic profile of wild stump-tailed macaques (Macaca arctoides) infected with malaria parasites in Thailand

RASopathies and cardiac manifestations

Contact Info

Product

Resources

About