title: The phenotype of human STK4 deficiency.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Hengameh
authors.initials: H
authors.lastname: Abdollahpour
authors.forename: Giridharan
authors.initials: G
authors.lastname: Appaswamy
authors.forename: Daniel
authors.initials: D
authors.lastname: Kotlarz
authors.forename: Jana
authors.initials: J
authors.lastname: Diestelhorst
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: E Michael
authors.initials: EM
authors.lastname: Gertz
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Hans H
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.forename: Karin R
authors.initials: KR
authors.lastname: Engelhardt
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Sabine
authors.initials: S
authors.lastname: Lohrmann
authors.forename: Roya
authors.initials: R
authors.lastname: Sherkat
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D007492:Iran / Q000453:epidemiology; D008297:Male; D009503:Neutropenia / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics*; D000099317:Hippo Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C095566:STK4 protein, human; D000099317:Hippo Kinases