Recurrent Infections and Immunodeficiency Caused by Severe Pancytopenia Associated with a Novel Life-Threatening Mutation in Hypoxia-Upregulated Protein 1

<i>HYOU1</i> encodes a protein from the endoplasmic reticulum chaperone proteins, expressed to protect cellular mechanisms from stress such as hypoxia, insufficient energy and excessive or insufficient substances, and to restore cell homeostasis. In this study, we report a novel pathogenic variant in <i>HYOU1</i>. The proband, the second patient with pathogenic variant in <i>HYOU1</i>, was a female born to consanguineous parents. A novel homozygous pathogenic variant in <i>HYOU1</i> (NM_001130991.3: c.1456C&gt;T; p.Arg486Cys) was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age. Both parents are heterozygous for this variant and have no issues related to this study.

<i>HYOU1</i> 编码内质网分子伴侣蛋白家族的一员，其表达可保护细胞机制免受缺氧、能量不足以及物质代谢过剩或匮乏等应激因素的侵害，并协助恢复细胞稳态。本研究报道了<i>HYOU1</i>基因中一种全新的致病性变异。该先证者是全球第二例携带<i>HYOU1</i>致病性变异的患者，为女性，其父母为近亲婚配。研究团队在该先证者体内检出<i>HYOU1</i>基因的全新纯合致病性变异（NM_001130991.3: c.1456C>T; p.Arg486Cys）。该变异导致患儿在出生后第2个月出现贫血、血小板减少症、重度全血细胞减少症与免疫缺陷，继而引发持续性高热、脑功能退行性改变及反复感染，最终患儿于3个半月时夭折。该变异的父母均为该位点的杂合携带者，未出现与本研究相关的临床异常。