Frontiers in Immunology (Nov 2024)
Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation
- 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
Affiliations
- Yu Huang
- National 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, China
- Yu Huang
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yu Huang
- Department of Hematology Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Lu Li
- National 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, China
- Lu Li
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Ran Chen
- National 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, China
- Ran Chen
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Lang Yu
- National 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, China
- Lang Yu
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Shunkai Zhao
- Department of Biology, School of Arts and Sciences, Tufts University, Medford, MA, United States
- Yanjun Jia
- National 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, China
- Yanjun Jia
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Ying Dou
- National 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, China
- Ying Dou
- Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Ying Dou
- Department of Hematology Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Zhiyong Zhang
- National 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, China
- Zhiyong Zhang
- Department of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yunfei An
- National 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, China
- Yunfei An
- Department of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xuemei Tang
- National 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, China
- Xuemei Tang
- Department of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xiaodong Zhao
- National 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, China
- Xiaodong Zhao
- Department of Rheumatism and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Lina Zhou
- National 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, China
- DOI
- https://doi.org/10.3389/fimmu.2024.1460990
- Journal volume & issue
-
Vol. 15
Abstract
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 and 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.
Keywords
