Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report
Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathological immune activation characterized by clinical signs and symptoms of extreme inflammation. It results from the uninhibited proliferation and activation of cells of the macrophage lineage and leads to the producti...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-06-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s43042-020-00067-3 |
| _version_ | 1818283678515593216 |
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| author | Mohamed Almalky Safaa H. A. Saleh Eman Gamal Baz Ahmed Elsadek Fakhr |
| author_facet | Mohamed Almalky Safaa H. A. Saleh Eman Gamal Baz Ahmed Elsadek Fakhr |
| author_sort | Mohamed Almalky |
| collection | DOAJ |
| description | Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathological immune activation characterized by clinical signs and symptoms of extreme inflammation. It results from the uninhibited proliferation and activation of cells of the macrophage lineage and leads to the production of excess amounts of pro-inflammatory cytokines. The familial form of HLH disease is due to mutations in several genes necessary for natural killer (NK) cell and T cell granule-mediated cytotoxic function. These genes are involved in sorting, trafficking, docking, and fusion of cytotoxic granules containing granzymes A and B and perforin to the cell membrane of the target cell (using the proteins LYST, AP-3 complex, Rab27a, Munc 13–4, Munc 18–2, syntaxin 11). Defect in any of those proteins results in defective cytotoxicity. Consequently, genes included in these steps play valuable roles in the pathogenesis of familial HLH disease including perforin (PRF1) gene in which defect causes familial HLH type 2 (FHL2). Case presentation A 2-year-old boy suffered from hepatosplenomegaly and fever. He fulfilled the required criteria for the diagnosis of HLH according to HLH-2004 diagnostic criteria. We screened the patient for the presence of mutations in the coding exons and of PRF1 gene by PCR amplification of genomic DNA followed by direct sequencing of the PCR products. We report a novel homozygous deletion/insertion frameshift mutation in PRF1 gene (M28393: exon 2: c.536delAinsCG p.F178fs). We treated him with HLH 2004 protocol of treatment and showed a remarkable response with resolution of fever and decrement in the size of hepatosplenomegaly. Conclusions Our study discovered a novel frameshift mutation in PRF1 gene in an infant with HLH disease, and it is the first report of this type of mutation in Egyptian patients with this disease. |
| first_indexed | 2024-12-13T00:40:44Z |
| format | Article |
| id | doaj.art-fb050f3839b44f129acc88b87dd381b8 |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-13T00:40:44Z |
| publishDate | 2020-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-fb050f3839b44f129acc88b87dd381b82022-12-22T00:05:08ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412020-06-012111510.1186/s43042-020-00067-3Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case reportMohamed Almalky0Safaa H. A. Saleh1Eman Gamal Baz2Ahmed Elsadek Fakhr3Pediatric Department, Faculty of Medicine, Zagazig UniversityPediatric Department, Faculty of Medicine, Zagazig UniversityPediatric Department, Faculty of Medicine, Zagazig UniversityMicrobiology and Immunology Department, Faculty of Medicine, Zagazig UniversityAbstract Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathological immune activation characterized by clinical signs and symptoms of extreme inflammation. It results from the uninhibited proliferation and activation of cells of the macrophage lineage and leads to the production of excess amounts of pro-inflammatory cytokines. The familial form of HLH disease is due to mutations in several genes necessary for natural killer (NK) cell and T cell granule-mediated cytotoxic function. These genes are involved in sorting, trafficking, docking, and fusion of cytotoxic granules containing granzymes A and B and perforin to the cell membrane of the target cell (using the proteins LYST, AP-3 complex, Rab27a, Munc 13–4, Munc 18–2, syntaxin 11). Defect in any of those proteins results in defective cytotoxicity. Consequently, genes included in these steps play valuable roles in the pathogenesis of familial HLH disease including perforin (PRF1) gene in which defect causes familial HLH type 2 (FHL2). Case presentation A 2-year-old boy suffered from hepatosplenomegaly and fever. He fulfilled the required criteria for the diagnosis of HLH according to HLH-2004 diagnostic criteria. We screened the patient for the presence of mutations in the coding exons and of PRF1 gene by PCR amplification of genomic DNA followed by direct sequencing of the PCR products. We report a novel homozygous deletion/insertion frameshift mutation in PRF1 gene (M28393: exon 2: c.536delAinsCG p.F178fs). We treated him with HLH 2004 protocol of treatment and showed a remarkable response with resolution of fever and decrement in the size of hepatosplenomegaly. Conclusions Our study discovered a novel frameshift mutation in PRF1 gene in an infant with HLH disease, and it is the first report of this type of mutation in Egyptian patients with this disease.http://link.springer.com/article/10.1186/s43042-020-00067-3Perforin (PRF1)Familial hemophagocytic lymphohistiocytosis 2 (FHL 2)Case reportNovel mutation |
| spellingShingle | Mohamed Almalky Safaa H. A. Saleh Eman Gamal Baz Ahmed Elsadek Fakhr Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report Egyptian Journal of Medical Human Genetics Perforin (PRF1) Familial hemophagocytic lymphohistiocytosis 2 (FHL 2) Case report Novel mutation |
| title | Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report |
| title_full | Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report |
| title_fullStr | Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report |
| title_full_unstemmed | Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report |
| title_short | Novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an Egyptian infant: case report |
| title_sort | novel mutation in perforin gene causing familial hemophagocytic lymphohistiocytosis type 2 in an egyptian infant case report |
| topic | Perforin (PRF1) Familial hemophagocytic lymphohistiocytosis 2 (FHL 2) Case report Novel mutation |
| url | http://link.springer.com/article/10.1186/s43042-020-00067-3 |
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