The phenotype of human STK4 deficiency
The phenotype of human STK4 deficiency
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DOI：
10.1182/blood-2011-09-378158
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发表时间：
2012-04-12
期刊：
影响因子：
20.3
通讯作者：
Klein, Christoph
中科院分区：
文献类型：
--
作者：
Abdollahpour, Hengameh;Appaswamy, Giridharan;Klein, Christoph
我们描述了一个新的临床表型相关的T和B细胞淋巴细胞减少症，间歇性中性粒细胞减少症，房间隔缺损的3名成员的血缘关系。他们的临床病史包括反复的细菌感染、病毒感染、皮肤粘膜念珠菌病、皮肤疣和皮肤脓肿。纯合性定位和候选基因测序揭示了基因STK 4（丝氨酸苏氨酸激酶4，以前具有符号MST 1）中的纯合性提前终止突变。STK 4是果蝇海马的人类直系同源物，是控制细胞生长和凋亡的高度保守途径的中心成分。STK 4缺陷的淋巴细胞和中性粒细胞表现出线粒体膜电位的损失增加和对凋亡的易感性增加。STK 4缺陷是一种新的人类原发性免疫缺陷综合征。（血。2012; 119（15）：3450-3457）
We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome. (Blood. 2012; 119(15):3450-3457)