title: Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency.
abstract: BACKGROUND
  Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established.
  
  
  METHODS
  A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 μg/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment.
  
  
  CONCLUSIONS
  Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency.
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: María T
authors.initials: MT
authors.lastname: Muñoz-Calvo
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pozo
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Gabriel Á
authors.initials: GÁ
authors.lastname: Martos-Moreno
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Federico
authors.initials: F
authors.lastname: Hawkins
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dauber
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Horacio M
authors.initials: HM
authors.lastname: Domené
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
mesh_terms: D002648:Child; D018388:Codon, Terminator; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006130:Growth Disorders / Q000188:drug therapy* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D011266:Pregnancy-Associated Plasma Protein-A / Q000172:deficiency* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D035781:Siblings; D016896:Treatment Outcome
chemical_list: D018388:Codon, Terminator; C583557:IGF1 protein, human; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A