Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation
BackgroundWHIM syndrome is a rare, autosomal dominant inborn error of immunity characterized by warts, hypogammaglobulinemia, infection, and myelokathexis. It is caused mainly by heterozygous mutations at the C-terminus of the C-X-C chemokine receptor type 4 (CXCR4) gene.MethodsWe described the deta...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460990/full |
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| author | Yu Huang Yu Huang Yu Huang Lu Li Lu Li Ran Chen Ran Chen Lang Yu Lang Yu Shunkai Zhao Yanjun Jia Yanjun Jia Ying Dou Ying Dou Ying Dou Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xiaodong Zhao Xiaodong Zhao Lina Zhou |
| author_facet | Yu Huang Yu Huang Yu Huang Lu Li Lu Li Ran Chen Ran Chen Lang Yu Lang Yu Shunkai Zhao Yanjun Jia Yanjun Jia Ying Dou Ying Dou Ying Dou Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xiaodong Zhao Xiaodong Zhao Lina Zhou |
| author_sort | Yu Huang |
| collection | DOAJ |
| description | BackgroundWHIM syndrome is a rare, autosomal dominant inborn error of immunity characterized by warts, hypogammaglobulinemia, infection, and myelokathexis. It is caused mainly by heterozygous mutations at the C-terminus of the C-X-C chemokine receptor type 4 (CXCR4) gene.MethodsWe described the detailed clinical, genetic, immunological and treatment characteristic of four WHIM patients from a single Chinese family.ResultsHere, we report four patients from a family carrying a variant of CXCR4 (c.1016_1017dupCT), which introduces a frameshift at codon V340, resulting in an extension of 14 amino acids (p.V340L fs*27). We provide an in-depth analysis of their clinical, genetic, immunological and treatment characteristic, noting that these patients exhibited an atypical clinical phenotype when compared to reported CXCR4R334X patients. Additionally, the frameshift variant CXCR4V340fs led to impaired receptor downregulation in patients’ PBMCs, and in HEK293T cells transfected with the variant plasmids.ConclusionsOur study provided detailed clinical features of four CXCR4V340fs WHIM patients from one Chinese family who presented atypical phenotype and enrich the spectrum of WHIM syndrome. |
| format | Article |
| id | doaj-art-9872af50823f499b94fd1f59fc7c5f13 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-9872af50823f499b94fd1f59fc7c5f132025-01-14T11:54:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14609901460990Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutationYu Huang0Yu Huang1Yu Huang2Lu Li3Lu Li4Ran Chen5Ran Chen6Lang Yu7Lang Yu8Shunkai Zhao9Yanjun Jia10Yanjun Jia11Ying Dou12Ying Dou13Ying Dou14Zhiyong Zhang15Zhiyong Zhang16Yunfei An17Yunfei An18Xuemei Tang19Xuemei Tang20Xiaodong Zhao21Xiaodong Zhao22Lina Zhou23National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematology Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Biology, School of Arts and Sciences, Tufts University, Medford, MA, United StatesNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematology Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaBackgroundWHIM syndrome is a rare, autosomal dominant inborn error of immunity characterized by warts, hypogammaglobulinemia, infection, and myelokathexis. It is caused mainly by heterozygous mutations at the C-terminus of the C-X-C chemokine receptor type 4 (CXCR4) gene.MethodsWe described the detailed clinical, genetic, immunological and treatment characteristic of four WHIM patients from a single Chinese family.ResultsHere, we report four patients from a family carrying a variant of CXCR4 (c.1016_1017dupCT), which introduces a frameshift at codon V340, resulting in an extension of 14 amino acids (p.V340L fs*27). We provide an in-depth analysis of their clinical, genetic, immunological and treatment characteristic, noting that these patients exhibited an atypical clinical phenotype when compared to reported CXCR4R334X patients. Additionally, the frameshift variant CXCR4V340fs led to impaired receptor downregulation in patients’ PBMCs, and in HEK293T cells transfected with the variant plasmids.ConclusionsOur study provided detailed clinical features of four CXCR4V340fs WHIM patients from one Chinese family who presented atypical phenotype and enrich the spectrum of WHIM syndrome.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460990/fullCXCR4 variantgain-of-functioninborn error of immunityWHIM syndromeheterogeneous phenotype |
| spellingShingle | Yu Huang Yu Huang Yu Huang Lu Li Lu Li Ran Chen Ran Chen Lang Yu Lang Yu Shunkai Zhao Yanjun Jia Yanjun Jia Ying Dou Ying Dou Ying Dou Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xiaodong Zhao Xiaodong Zhao Lina Zhou Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation Frontiers in Immunology CXCR4 variant gain-of-function inborn error of immunity WHIM syndrome heterogeneous phenotype |
| title | Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation |
| title_full | Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation |
| title_fullStr | Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation |
| title_full_unstemmed | Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation |
| title_short | Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation |
| title_sort | heterogeneous phenotype of a chinese familial whim syndrome with cxcr4v340fs gain of function mutation |
| topic | CXCR4 variant gain-of-function inborn error of immunity WHIM syndrome heterogeneous phenotype |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460990/full |
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