{"title":"一个患有新型 RAC2 p.I21S 显性激活突变的家族的表型谱","authors":"Louisa Ashby, Lydia Chan, Christine Winterbourn, See-Tarn Woon, Paula Keating, Raoul Heller, Rohan Ameratunga, Ignatius Chua, Kuang-Chih Hsiao","doi":"10.1002/cti2.1493","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Dominant-activating (DA) lesions in <i>RAC2</i> have been reported in 18 individuals to date. Some have required haematopoietic stem cell transplantation (HSCT) for their (severe) combined immunodeficiency syndrome phenotype. We aimed to investigate clinical and cellular features of a kindred harbouring a novel variant in <i>RAC2</i> p.Ile21Ser (I21S) to better understand DA lesions' phenotypic spectrum.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Clinical and immunological information was collated for seven living individuals from the same kindred with <i>RAC2</i> p.I21S. We evaluated neutrophil morphology, RAC2 protein expression and superoxide production using freshly isolated neutrophils stimulated with phorbol-12-myristate-13-acetate (PMA) and N-formyl-MetLeuPhe (fMLP).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Patient 1 (P1, aged 11, male) has a history of bacterial suppurative otitis media, viral and bacterial cutaneous infections. P1's siblings (P2, P3), mother (P4), maternal aunt (P5) and uncle (P6) have similar infection histories. P1's maternal cousin (P7) presented with Burkitt's lymphoma at age 9. All affected individuals are alive and none has required HSCT to date. They have chronic lymphopenia affecting the CD4<sup>+</sup>T and B-cell compartments. P1–3 have isolated reduction in IgM levels whereas the adults universally have normal immunoglobulins. Specific antibody responses are preserved. Affected individuals have neutrophil vacuolation, and their neutrophils have enhanced superoxide production compared to healthy controls.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p><i>RAC2</i> p.I21S is an activating variant causing notable morphological and functional abnormalities similar to other reported DA mutations. This novel variant expands the broad clinical phenotypic spectrum of <i>RAC2</i> DA lesions, emphasising the need to tailor clinical management according to patients' disease phenotype and severity.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 2","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1493","citationCount":"0","resultStr":"{\"title\":\"Phenotypic spectrum in a family with a novel RAC2 p.I21S dominant-activating mutation\",\"authors\":\"Louisa Ashby, Lydia Chan, Christine Winterbourn, See-Tarn Woon, Paula Keating, Raoul Heller, Rohan Ameratunga, Ignatius Chua, Kuang-Chih Hsiao\",\"doi\":\"10.1002/cti2.1493\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Dominant-activating (DA) lesions in <i>RAC2</i> have been reported in 18 individuals to date. Some have required haematopoietic stem cell transplantation (HSCT) for their (severe) combined immunodeficiency syndrome phenotype. We aimed to investigate clinical and cellular features of a kindred harbouring a novel variant in <i>RAC2</i> p.Ile21Ser (I21S) to better understand DA lesions' phenotypic spectrum.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Clinical and immunological information was collated for seven living individuals from the same kindred with <i>RAC2</i> p.I21S. We evaluated neutrophil morphology, RAC2 protein expression and superoxide production using freshly isolated neutrophils stimulated with phorbol-12-myristate-13-acetate (PMA) and N-formyl-MetLeuPhe (fMLP).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Patient 1 (P1, aged 11, male) has a history of bacterial suppurative otitis media, viral and bacterial cutaneous infections. P1's siblings (P2, P3), mother (P4), maternal aunt (P5) and uncle (P6) have similar infection histories. P1's maternal cousin (P7) presented with Burkitt's lymphoma at age 9. All affected individuals are alive and none has required HSCT to date. They have chronic lymphopenia affecting the CD4<sup>+</sup>T and B-cell compartments. P1–3 have isolated reduction in IgM levels whereas the adults universally have normal immunoglobulins. Specific antibody responses are preserved. Affected individuals have neutrophil vacuolation, and their neutrophils have enhanced superoxide production compared to healthy controls.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p><i>RAC2</i> p.I21S is an activating variant causing notable morphological and functional abnormalities similar to other reported DA mutations. This novel variant expands the broad clinical phenotypic spectrum of <i>RAC2</i> DA lesions, emphasising the need to tailor clinical management according to patients' disease phenotype and severity.</p>\\n </section>\\n </div>\",\"PeriodicalId\":152,\"journal\":{\"name\":\"Clinical & Translational Immunology\",\"volume\":\"13 2\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-02-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1493\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Translational Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1493\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1493","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
迄今为止,已有18人报告了RAC2的显性激活(DA)病变。其中一些人需要进行造血干细胞移植(HSCT)来治疗其(重度)联合免疫缺陷综合征表型。我们的目的是调查一个携带 RAC2 p.Ile21Ser (I21S) 新型变异体的同类的临床和细胞特征,以更好地了解 DA 病变的表型谱。
Phenotypic spectrum in a family with a novel RAC2 p.I21S dominant-activating mutation
Objectives
Dominant-activating (DA) lesions in RAC2 have been reported in 18 individuals to date. Some have required haematopoietic stem cell transplantation (HSCT) for their (severe) combined immunodeficiency syndrome phenotype. We aimed to investigate clinical and cellular features of a kindred harbouring a novel variant in RAC2 p.Ile21Ser (I21S) to better understand DA lesions' phenotypic spectrum.
Methods
Clinical and immunological information was collated for seven living individuals from the same kindred with RAC2 p.I21S. We evaluated neutrophil morphology, RAC2 protein expression and superoxide production using freshly isolated neutrophils stimulated with phorbol-12-myristate-13-acetate (PMA) and N-formyl-MetLeuPhe (fMLP).
Results
Patient 1 (P1, aged 11, male) has a history of bacterial suppurative otitis media, viral and bacterial cutaneous infections. P1's siblings (P2, P3), mother (P4), maternal aunt (P5) and uncle (P6) have similar infection histories. P1's maternal cousin (P7) presented with Burkitt's lymphoma at age 9. All affected individuals are alive and none has required HSCT to date. They have chronic lymphopenia affecting the CD4+T and B-cell compartments. P1–3 have isolated reduction in IgM levels whereas the adults universally have normal immunoglobulins. Specific antibody responses are preserved. Affected individuals have neutrophil vacuolation, and their neutrophils have enhanced superoxide production compared to healthy controls.
Conclusion
RAC2 p.I21S is an activating variant causing notable morphological and functional abnormalities similar to other reported DA mutations. This novel variant expands the broad clinical phenotypic spectrum of RAC2 DA lesions, emphasising the need to tailor clinical management according to patients' disease phenotype and severity.
期刊介绍:
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.