Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4 V340fs gain-of-function mutation.

Autor:	Huang Y; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.; Department of Hematology Oncology, Children's Hospital of Chongqing Medical University, Chongqing, China., Li L; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China., Chen R; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China., Yu L; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhao S; Department of Biology, School of Arts and Sciences, Tufts University, Medford, MA, United States., Jia Y; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China., Dou Y; 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.; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.; Department of Hematology Oncology, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhang Z; 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.; Department of Rheumatism and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., An Y; 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.; Department of Rheumatism and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Tang X; 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.; Department of Rheumatism and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhao X; 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.; Department of Rheumatism and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhou L; 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.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Nov 07; Vol. 15, pp. 1460990. Date of Electronic Publication: 2024 Nov 07 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1460990
Abstrakt:	Background: WHIM 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. Methods: We described the detailed clinical, genetic, immunological and treatment characteristic of four WHIM patients from a single Chinese family. Results: Here, 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 CXCR4 R334X patients. Additionally, the frameshift variant CXCR4 V340fs led to impaired receptor downregulation in patients' PBMCs, and in HEK293T cells transfected with the variant plasmids. Conclusions: Our study provided detailed clinical features of four CXCR4 V340fs WHIM patients from one Chinese family who presented atypical phenotype and enrich the spectrum of WHIM syndrome. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Huang, Li, Chen, Yu, Zhao, Jia, Dou, Zhang, An, Tang, Zhao and Zhou.)
Databáze:	MEDLINE
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