title: Lack of expression of SERPINF1, the gene coding for pigment epithelium-derived factor, causes progressively deforming osteogenesis imperfecta with normal type I collagen.
abstract: Osteogenesis imperfecta (OI) is a clinically heterogeneous heritable connective tissue disorder, characterized by low bone mass and reduced strength, which result in susceptibility to fracture and bone deformities. In most cases it is caused by dominant mutations in type I collagen genes, COL1A1 and COL1A2. Recessive forms, which collectively account for approximately 5% of cases of osteogenesis imperfecta detected in North America and Europe, are caused instead by mutations in various genes coding for proteins involved in collagen posttranslational modifications, folding, and secretion. A novel disease locus, SERPINF1, coding for pigment epithelium-derived factor (PEDF), has been found recently. In SERPINF1 mutants described so far, synthesis, posttranslational modification, and secretion of type I collagen were reported to be normal. Here we describe three siblings born to consanguineous parents, who show an initially mild and then progressively worsening form of OI with severe deformities of the long bones. They are homozygous for a frameshift mutation in exon 4 of the SERPINF1 gene, which leads to lack of the transcription/translation product, likely a key factor in bone deposition and remodeling. Synthesis and secretion of type I collagen are normal. Clinical, radiographic, histological, and histomorphometric data from the proband are reminiscent of the distinctive features of type VI OI.
authors: Department of Life and Reproduction Sciences and Paediatric Clinic, University of Verona, Verona, Italy.
authors: Giacomo
authors: G
authors: Venturi
authors: Alberto
authors: A
authors: Gandini
authors: Elena
authors: E
authors: Monti
authors: Luca
authors: L
authors: Dalle Carbonare
authors: Massimiliano
authors: M
authors: Corradi
authors: Monica
authors: M
authors: Vincenzi
authors: Maria Teresa
authors: MT
authors: Valenti
authors: Maurizia
authors: M
authors: Valli
authors: Enrico
authors: E
authors: Pelilli
authors: Attilio
authors: A
authors: Boner
authors: Monica
authors: M
authors: Mottes
authors: Franco
authors: F
authors: Antoniazzi
mesh_terms: D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism*; D018450:Disease Progression; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D015843:Serpins / Q000235:genetics*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D024042:Collagen Type I; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor