title: Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families.
abstract: Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder characterized by bone fragility. It is one of the rare forms of skeletal deformity caused by sequence variants in at least 14 different genes, including FKBP10 (MIM 607063) encoding protein FKBP65. Here we present three consanguineous families of Pakistani origin segregating OI in an autosomal-recessive pattern. Genotyping using either single-nucleotide polymorphism markers by Affymetrix GeneChip Human Mapping 250K Nsp array or polymorphic microsatellite markers revealed a homozygous region, containing a candidate gene FKBP10, among affected members on chromosome 17q21.2. Sequencing the FKBP10 gene revealed a homozygous novel nonsense variant (c.1490G>A, p.Trp497*) in the family A and two previously reported variants, including a missense (c.344G>A, p.Arg115Gln), in the family B and duplication of a nucleotide C (c.831dupC, p.Gly278ArgfsX295) in the family C. Our findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Umair
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Annum
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Kohat University of Science and Technology (KUST), Khyber Pakhtunkhwa Province of Pakistan, Pakistan.
authors.forename: Abid
authors.initials: A
authors.lastname: Jan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Farooq
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imran
authors.affiliation: Center for Genetics and Inherited Diseases, Taibah University Al Madinah Al Munawarah, Munawarah, Saudi Arabia.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Samman
authors.affiliation: Center for Genetics and Inherited Diseases, Taibah University Al Madinah Al Munawarah, Munawarah, Saudi Arabia.
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Pakistan Academy of Sciences (PAS), Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D003241:Consanguinity; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree; D022021:Tacrolimus Binding Proteins / Q000235:genetics*
chemical_list: D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human