Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report
<h3>Background</h3><p dir="ltr">Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-c...
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2023
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| _version_ | 1864513521210884096 |
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| author | Fawzia M. Elgharbawy (17045534) |
| author2 | Mohammed Yousuf Karim (17045535) Dina Sameh Soliman (17045537) Amel Siddik Hassan (17045539) Anoop Sudarsanan (17045544) Ashraf Gad (17040114) |
| author2_role | author author author author author |
| author_facet | Fawzia M. Elgharbawy (17045534) Mohammed Yousuf Karim (17045535) Dina Sameh Soliman (17045537) Amel Siddik Hassan (17045539) Anoop Sudarsanan (17045544) Ashraf Gad (17040114) |
| author_role | author |
| dc.creator.none.fl_str_mv | Fawzia M. Elgharbawy (17045534) Mohammed Yousuf Karim (17045535) Dina Sameh Soliman (17045537) Amel Siddik Hassan (17045539) Anoop Sudarsanan (17045544) Ashraf Gad (17040114) |
| dc.date.none.fl_str_mv | 2023-10-12T08:03:56Z |
| dc.identifier.none.fl_str_mv | 10.57945/manara.24197715.v1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/poster/Neonatal_autoimmune_lymphoproliferative_syndrome_with_a_novel_pathogenic_homozygous_FAS_variant_effectively_treated_with_sirolimus_Case_report/24197715 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Immunology Paediatrics ALPS (autoimmune lymphoproliferative syndrome) DNT-cells sirolimus FAS novel variant newborn |
| dc.title.none.fl_str_mv | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| dc.type.none.fl_str_mv | Image Poster info:eu-repo/semantics/publishedVersion image |
| description | <h3>Background</h3><p dir="ltr">Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.</p><h3>Case presentation</h3><p dir="ltr">We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.</p><h3>Conclusion</h3><p dir="ltr">We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient’s clinical symptoms.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_40e5f740da8f2b141207e128a15acd47 |
| identifier_str_mv | 10.57945/manara.24197715.v1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24197715 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case reportFawzia M. Elgharbawy (17045534)Mohammed Yousuf Karim (17045535)Dina Sameh Soliman (17045537)Amel Siddik Hassan (17045539)Anoop Sudarsanan (17045544)Ashraf Gad (17040114)Biological sciencesGeneticsBiomedical and clinical sciencesImmunologyPaediatricsALPS (autoimmune lymphoproliferative syndrome)DNT-cellssirolimusFASnovel variantnewborn<h3>Background</h3><p dir="ltr">Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.</p><h3>Case presentation</h3><p dir="ltr">We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.</p><h3>Conclusion</h3><p dir="ltr">We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient’s clinical symptoms.</p>2023-10-12T08:03:56ZImagePosterinfo:eu-repo/semantics/publishedVersionimage10.57945/manara.24197715.v1https://figshare.com/articles/poster/Neonatal_autoimmune_lymphoproliferative_syndrome_with_a_novel_pathogenic_homozygous_FAS_variant_effectively_treated_with_sirolimus_Case_report/24197715CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/241977152023-10-12T08:03:56Z |
| spellingShingle | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report Fawzia M. Elgharbawy (17045534) Biological sciences Genetics Biomedical and clinical sciences Immunology Paediatrics ALPS (autoimmune lymphoproliferative syndrome) DNT-cells sirolimus FAS novel variant newborn |
| status_str | publishedVersion |
| title | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| title_full | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| title_fullStr | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| title_full_unstemmed | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| title_short | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| title_sort | Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus: Case report |
| topic | Biological sciences Genetics Biomedical and clinical sciences Immunology Paediatrics ALPS (autoimmune lymphoproliferative syndrome) DNT-cells sirolimus FAS novel variant newborn |