A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III

Roman Crazzolara; Kathrin Maurer; Harald Schulze; Barbara Zieger; Jozef Zustin; Ansgar S Schulz

doi:10.1002/pbc.25537

A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III

Pediatr Blood Cancer. 2015 Sep;62(9):1677-9. doi: 10.1002/pbc.25537. Epub 2015 Apr 8.

Authors

Roman Crazzolara¹, Kathrin Maurer¹, Harald Schulze², Barbara Zieger³, Jozef Zustin⁴, Ansgar S Schulz⁵

Affiliations

¹ Department for Pediatrics, Medical University Innsbruck, Innsbruck, Austria.
² Department of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.
³ Department of Paediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.
⁴ Institute of Pathology, University of Münster, Münster, Germany.
⁵ Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.

PMID: 25854317
DOI: 10.1002/pbc.25537

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.

Keywords: KINDLIN-3; LAD-III; leukocytosis; osteopetrosis; platelet malfunction.

Publication types

Case Reports

MeSH terms

Blood Platelets / physiology*
Bone Marrow Transplantation
Bone Resorption / genetics*
Bone Resorption / pathology
Cell Adhesion
Cell Nucleus / ultrastructure
Codon, Nonsense*
Exons / genetics
Female
Hemorrhagic Disorders / genetics
Homeostasis
Humans
Infant, Newborn
Integrins / physiology*
Leukocyte-Adhesion Deficiency Syndrome / genetics*
Leukocyte-Adhesion Deficiency Syndrome / pathology
Leukocyte-Adhesion Deficiency Syndrome / therapy
Leukocytes / physiology*
Membrane Proteins / deficiency
Membrane Proteins / genetics*
Membrane Proteins / physiology
Mutation, Missense*
Neoplasm Proteins / deficiency
Neoplasm Proteins / genetics*
Neoplasm Proteins / physiology
Osteoclasts / physiology*
Osteoclasts / ultrastructure
Osteopetrosis / genetics*
Osteopetrosis / pathology
Osteopetrosis / therapy
Platelet Aggregation / genetics
Point Mutation*
Remission Induction

Substances

Codon, Nonsense
FERMT3 protein, human
Integrins
Membrane Proteins
Neoplasm Proteins

Supplementary concepts

Leukocyte Adhesion Deficiency, Type III