title: Hematopoietic stem cell transplantation corrects osteopetrosis in a child carrying a novel homozygous mutation in the FERMT3 gene.
abstract: Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments. Because of the severe presentation at birth, the patient received Hematopoietic Stem Cell Transplantation (HSCT) at 2months of age with successful outcome. Post-HSCT genetic investigation by means of exome sequencing identified a novel homozygous mutation in the Fermitin Family Member 3 (FERMT3) gene, which was predicted to disrupt the functionality of its protein product kindlin 3. Our report provides information relevant to physicians for recognizing patients with one of the rarest forms of infantile malignant OPT, and clearly demonstrates that HSCT cures kindlin 3 deficiency with severe phenotype.
authors.affiliation: Humanitas Clinical and Research Institute, Rozzano, Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Palagano
authors.affiliation: Bone Marrow Transplantation Unit, Great North Children's Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: CRS4, Science and Technology Park Polaris, Pula, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Uva
authors.affiliation: Humanitas Clinical and Research Institute, Rozzano, Italy; CNR-IRGB, Milan Unit, Milan, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Menale
authors.affiliation: Humanitas Clinical and Research Institute, Rozzano, Italy; CNR-IRGB, Milan Unit, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.affiliation: Bone Marrow Transplantation Unit, Great North Children's Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: Mario.Abinun@nuth.nhs.uk.
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.affiliation: Humanitas Clinical and Research Institute, Rozzano, Italy; CNR-IRGB, Milan Unit, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sobacchi
mesh_terms: D002648:Child; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D010641:Phenotype
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: Bleeding; Integrin; Osteoclast