title: A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III.
abstract: Disabling mutations in integrin-mediated cell signaling have been a major focus of interest over the last decade for patients affected with leukocyte adhesion deficiency-III (LAD-III). In this study, we identified a new C>T point mutation in exon 13 in the FERMT3 gene in an infant diagnosed with LAD-III and showed that KINDLIN-3 expression is required for platelet aggregation and leukocyte function, but also osteoclast-mediated bone resorption. After allogeneic bone marrow transplant, all overt symptoms disappeared. This newly identified mutation along with its novel role in dysregulation of bone homeostasis extends our understanding of KINDLIN-3 in humans.
authors: Department for Pediatrics, Medical University Innsbruck, Innsbruck, Austria.
authors: Roman
authors: R
authors: Crazzolara
authors: Department for Pediatrics, Medical University Innsbruck, Innsbruck, Austria.
authors: Kathrin
authors: K
authors: Maurer
authors: Department of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.
authors: Harald
authors: H
authors: Schulze
authors: Department of Paediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors: Barbara
authors: B
authors: Zieger
authors: Institute of Pathology, University of Münster, Münster, Germany.
authors: Jozef
authors: J
authors: Zustin
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors: Ansgar S
authors: AS
authors: Schulz
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D016026:Bone Marrow Transplantation; D001862:Bone Resorption / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000648:ultrastructure; D018389:Codon, Nonsense; D005091:Exons / Q000235:genetics; D005260:Female; D006474:Hemorrhagic Disorders / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D007231:Infant, Newborn; D016023:Integrins / Q000502:physiology*; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007962:Leukocytes / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology* / Q000648:ultrastructure; D010022:Osteopetrosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D010974:Platelet Aggregation / Q000235:genetics; D017354:Point Mutation; D012074:Remission Induction
chemical_list: D018389:Codon, Nonsense; C477322:FERMT3 protein, human; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: KINDLIN-3; LAD-III; leukocytosis; osteopetrosis; platelet malfunction