The novel p.Gly306Asp perforin mutation causes Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL-2) probably due to a critical role of Gly306 in the pore-forming perforin domain
| Autor: | Maria Alonso-Martinez, Carmen Rodríguez-Sainz, Ana Fernández-Teijeiro, Susana García-Obregón, Itziar Astigarraga, Juana Gil-Herrera, Lydia Martin-Martin, Ramon Urrea Moreno |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | LymphoSign Journal. |
| ISSN: | 2292-5945 2292-5937 |
| DOI: | 10.14785/lymphosign-2017-0006 |
| Popis: | Background: Three substitutions at either Gly305 or Gly306 within the membrane attack/complex perforin domain (MACPF) of perforin have been previously identified in a number of patients with hemophagocytic lymphohistiocytosis (HLH). However, their pathogenic impact remains unclear since all the cases reported so far carried heterozygous genotypes and showed very heterogeneous clinical presentations. Here, we report a new substitution (p.Gly306Asp) and use in silico tools to elucidate the pathogenic mechanisms and severity associated with human Gly306 and Gly305 mutations.Methods: The immunological workup included perforin expression and perforin gene (PRF1) mutation analysis. Computer algorithms based on conservation, secondary, and tertiary protein structure analyses were applied to assess the role of the mutations in disease pathogenesis.Results: In our patient, we found a previously undescribed homozygous c. 917G>A (p.Gly306Asp) mutation in the PRF1 gene that was associated with null perforin expressio... |
| Databáze: | OpenAIRE |
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