The phenotype of human STK4 deficiency

被引：273

作者：

Abdollahpour, Hengameh ^{[2
]}

Appaswamy, Giridharan ^{[2
]}

Kotlarz, Daniel ^{[1
,2
]}

Diestelhorst, Jana ^{[1
,2
]}

Beier, Rita ^{[2
]}

Schaeffer, Alejandro A. ^{[3
]}

Gertz, E. Michael ^{[3
]}

Schambach, Axel ^{[4
]}

Kreipe, Hans H. ^{[5
]}

Pfeifer, Dietmar ^{[6
]}

Engelhardt, Karin R. ^{[7
,8
]}

Rezaei, Nima ^{[9
]}

Grimbacher, Bodo ^{[7
,8
]}

Lohrmann, Sabine ^{[10
]}

Sherkat, Roya ^{[11
]}

Klein, Christoph ^{[1
,2
]}

机构：

[1] Dr von Haunersches Kinderspital, Univ Childrens Hosp Munich, D-80337 Munich, Germany

[2] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany

[3] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[4] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany

[5] Hannover Med Sch, Inst Pathol, D-3000 Hannover, Germany

[6] Univ Freiburg, Med Ctr, Dept Hematol Oncol, Core Facil Genom 2, Freiburg, Germany

[7] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England

[8] UCL, London, England

[9] Univ Tehran Med Sci, Childrens Med Ctr, Pediat Ctr Excellence, Res Ctr Immunodeficiencies, Tehran, Iran

[10] Hannover Med Sch, Dept Pediat Cardiol, D-3000 Hannover, Germany

[11] Isfahan Univ Med Sci, Dept Infect Dis, Infect Dis Res Ctr, Esfahan, Iran

来源：

BLOOD | 2012年 / 119卷 / 15期

基金：

美国国家卫生研究院;

关键词：

ORGAN SIZE CONTROL; CONGENITAL NEUTROPENIA; OXIDATIVE-STRESS; CASPASE CLEAVAGE; KINASE MST1; APOPTOSIS; PHOSPHORYLATION; ACTIVATION; MUTATIONS; PATHWAY;

D O I：

10.1182/blood-2011-09-378158

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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)

引用

页码：3450 / 3457

页数：8

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