PDF(Pubmed)
Abstract：
Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is a rare, combined immunodeficiency disease predominantly caused by gain-of-function variants in the CXCR4 gene that typically results in truncation of the carboxyl terminus of C-X-C chemokine receptor type 4 (CXCR4) leading to impaired leukocyte egress from bone marrow to peripheral blood. Diagnosis of WHIM syndrome continues to be challenging and is often made through clinical observations and/or genetic testing. Detection of a pathogenic CXCR4 variant in an affected individual supports the diagnosis of WHIM syndrome but relies on an appropriate annotation of disease-causing variants. Understanding the genotypic-phenotypic associations in WHIM syndrome has the potential to improve time to diagnosis and guide appropriate clinical management, resulting in a true example of precision medicine. This article provides an overview of the spectrum of CXCR4 variants in WHIM syndrome and summarizes the various lines of clinical and functional evidence that can support interpretation of newly identified variants.
摘要：
疣,低丙种球蛋白血症，感染,髓鞘综合征（WHIM）是一种罕见的，联合免疫缺陷病主要由CXCR4基因的功能获得变异体引起,该变异体通常导致C-X-C趋化因子受体4型(CXCR4)羧基末端截短,导致白细胞从骨髓向外周血的流出受损.WHIM综合征的诊断仍然具有挑战性，通常通过临床观察和/或基因检测来进行。在受影响的个体中检测致病性CXCR4变体支持WHIM综合征的诊断，但依赖于对致病变体的适当注释。了解WHIM综合征的基因型-表型相关性有可能缩短诊断时间并指导适当的临床治疗。产生了精准医学的真正例子。本文概述了WHIM综合征中CXCR4变体的频谱，并总结了可以支持新鉴定的变体解释的各种临床和功能证据。
