Navegando por Palavras-chave "Receptor TiE2"

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    Caracterização funcional das variantes p.Q370H e p.R384Q presentes no gene ANGPT1
    (Universidade Federal de São Paulo (UNIFESP), 2020-11-26) Leite, Caroliny De Sousa [UNIFESP]; Pesquero, Joao Bosco [UNIFESP]; Universidade Federal de São Paulo
    Introduction:Hereditary angioedema (HAE) is characterized by sudden episodes of swelling that cause pain, discomfort and, according to its location, can disfigure the patient. Edema affects mainly the upper and lower extremities (hands and feet), gastrointestinal tract, genitalia and face. If not treated it can lead to death due to laryngeal edema. HAE is an autosomal dominant disorder mainly caused by mutations in C1 esterase inhibitor gene (SERPING1), leading to an overproduction of bradykinin, or as a result of specific mutations in the F12, ANGPT1, PLG, KNG1 or MYOF genes. However, many patients with HAE do not present any mutation in these two genes, being classified as HAE with unknown causes (U-HAE) patients. Aim: This work aimed to clinically investigate and characterize patients diagnosed with HAE-U and analyze the impact of mutations found in the ANGPT1 gene in vitro. Methods: For clinical characterization, the history of the patients was evaluated regarding the location of the edema, crises triggering factors, onset of symptoms and time of delay in diagnosis. The ANGPT1 gene containing the target mutations was cloned and expressed in eukaryotic cells. Proteins containing the mutation were evaluated by functional permeability assays. Results: Two heterozygous missense mutations were found in exon 7 of the angiopoietin 1 gene (p.Q370H and p.R384Q). Most patients had subcutaneous edema affecting the extremities (face, lips, eyelids and genitalia). As for the triggering factors, stress was identified as the main cause. The mean age at onset of symptoms was 16.5 years in patients carrying ANGPT1 mutations and 27.4 years in AEH-U patients. Maximum age at onset of symptoms was 45 years in the ANGPT1-mutations group and 86 years in the HAE-U group. In silico analysis indicate that the variants are found in the fibrinogen domain of ANGPT1, specifically in subdomain B, and do not participate in the interaction site with TiE2 receptor Conclusion: A possible molecular diagnosis for patients belonging to the HAE-U group might be suggested, reinforcing the need to include the ANGPT1 gene as a marker to the molecular diagnosis of HAE. In vitro analysis were not conclusive and further studies are required. studies are required.