title: Clinical and molecular analysis in families with autosomal recessive osteogenesis imperfecta identifies mutations in five genes and suggests genotype-phenotype correlations.
abstract: Autosomal recessive osteogenesis imperfecta (AR-OI) is an inherited condition which in recent years has been shown with increasing genetic and clinical heterogeneity. In this article, we performed clinical assessment and sought mutations in patients from 10 unrelated families with AR-OI, one of whom was presented with the additional features of Bruck syndrome (BS). Pathogenic changes were identified in five different genes: three families had mutations in FKBP10, three in SERPINF1, two in LEPRE1, one in CRTAP, and one in PPIB. With the exception of a FKBP10 mutation in the BS case, all changes are novel. Of note, insertion of an AluYb8 repetitive element was detected in exon 6 of SERPINF1. Since the studied patients had variable manifestations and some distinctive features, genotype/phenotype correlations are suggested.
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Caparrós-Martin
authors.forename: María
authors.initials: M
authors.lastname: Valencia
authors.forename: Veronica
authors.initials: V
authors.lastname: Pulido
authors.forename: Victor
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rueda-Arenas
authors.forename: Khalda
authors.initials: K
authors.lastname: Amr
authors.forename: Chantal
authors.initials: C
authors.lastname: Farra
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Victor L
authors.initials: VL
authors.lastname: Ruiz-Perez
authors.forename: Samia
authors.initials: S
authors.lastname: Temtamy
authors.forename: Mona
authors.initials: M
authors.lastname: Aglan
mesh_terms: D000293:Adolescent; D020087:Alu Elements / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics; D021983:Cyclophilins / Q000235:genetics*; D004164:Diphosphonates / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D064828:Prolyl Hydroxylases; D011509:Proteoglycans / Q000235:genetics*; D011859:Radiography; D017422:Sequence Analysis, DNA; D015843:Serpins / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D024042:Collagen Type I; D021983:Cyclophilins; D004164:Diphosphonates; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009414:Nerve Growth Factors; D064828:Prolyl Hydroxylases; D011509:Proteoglycans; D015843:Serpins; D022021:Tacrolimus Binding Proteins; D000099174:Pigment Epithelium-Derived Factor; C108053:CRTAP protein, human; C081786:cyclophilin B; C485657:P3H1 protein, human; C110054:FKBP10 protein, human