在感染 SARS-CoV-2 的情况下,由新型 LYST 复合突变引起的晚发性青少年切迪克-希加希综合征患者的病情加速发展

IF 2.1 4区 医学 Q3 HEMATOLOGY
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引用次数: 0

摘要

切迪克-希加希综合征(CHS)是一种罕见的常染色体隐性遗传疾病,以严重的免疫缺陷、白化病和凝血功能障碍为特征。这种毁灭性疾病多在儿童早期诊断,与溶酶体异常有关,原因是 CHS1/LYST 基因突变导致溶酶体转运调节因子缺失或功能受损。在本研究中,我们报告了一例由两个新型复合杂合子 CHS1/LYST 突变引起的晚发型 CHS:c.8407C >T,导致残基 Gln2803 翻译提前终止(p. Gln2803Ter),以及一个小缺失 c.4020_4031del,导致三个氨基酸残基的框内缺失(p. Asp1343_Val1346del)。这两个变体都保留了 CHS/LYST 蛋白的大部分,尤其是 p. Asp1343_Val1346del,它保留了 C 端关键的 BEACH 和 WD40 功能域,有可能保持残余活性并减轻患者症状。SARS-CoV-2 感染的时间线和症状的快速发展表明,病毒感染可能引发了加速期的发展,导致预后不良。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Accelerated phase development in a late-onset adolescent Chediak-Higashi syndrome patient caused by compound novel LYST mutations in the setting of SARS-CoV-2 infection

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive genetic disorder characterized by severe immunodeficiency, albinism and coagulation deficiency. Mostly diagnosed in early childhood, this devastating condition is associated with lysosomal abnormalities attributed to the absence or impaired function of lysosomal trafficking regulator caused by mutations in the CHS1/LYST gene. In current study, we report a case of late-onset CHS caused by two novel compound heterozygous CHS1/LYST mutations: c.8407C > T, leading to early termination of translation at residue Gln2803 (p. Gln2803Ter), and a small deletion c. 4020_4031del, resulting in an in-frame deletion of three amino acid residues (p. Asp1343_Val1346del). Both variants retain a large part of the CHS/LYST protein, particularly p. Asp1343_Val1346del, which preserves critical functional BEACH and WD40 domains in the C terminal, potentially maintaining residual activity and alleviating patient symptoms. The timeline of SARS-CoV-2 infection and rapid symptom progression suggests that the viral infection may have trigger the accelerated phase development leading to a poor prognosis.

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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
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