Abstract：
To evaluate a novel candidate disease gene, we engaged international collaborators and identified rare, biallelic, specifically homozygous, loss of function variants in SENP7 in 4 children from 3 unrelated families presenting with neurodevelopmental abnormalities, dysmorphism, and immunodeficiency. Their clinical presentations were characterized by hypogammaglobulinemia, intermittent neutropenia, and ultimately death in infancy for all 4 patients. SENP7 is a sentrin-specific protease involved in posttranslational modification of proteins essential for cell regulation, via a process referred to as deSUMOylation. We propose that deficiency of deSUMOylation may represent a novel mechanism of primary immunodeficiency.
摘要：
为了评估一种新的候选疾病基因，我们邀请了国际合作者，并确定了罕见的，双等位基因,特别是纯合的，来自三个无关家庭的四个儿童的SENP7功能变异丧失，表现为神经发育异常，畸形,和免疫缺陷。他们的临床表现以低丙种球蛋白血症为特征，间歇性中性粒细胞减少症,最终四名患者在婴儿期死亡。SENP7是一种sentrin特异性蛋白酶，参与细胞调节所必需的蛋白质的翻译后修饰，通过称为去SUMO化的过程。我们认为去SUMO化的缺乏可能代表了原发性免疫缺陷的新机制。
