Get access

Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta

Authors

  • Encarna Guillén-Navarro,

    Corresponding author
    1. Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
    2. Cátedra de Genética Médica, Universidad Católica de San Antonio (UCAM), Murcia, Spain
    3. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    • Correspondence to:

      Victor L. Ruiz-Perez, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain.

      E-mail: vlruiz@iib.uam.es

      Correspondence to:

      Encarna Guillén-Navarro; Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia, Spain.

      E-mail: guillen.encarna@gmail.com

    Search for more papers by this author
  • María Juliana Ballesta-Martínez,

    1. Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    Search for more papers by this author
  • María Valencia,

    1. Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain
    Search for more papers by this author
  • Ana María Bueno,

    1. Department of Orthopedic Surgery, Hospital Universitario de Getafe, Madrid, Spain
    Search for more papers by this author
  • Victor Martinez-Glez,

    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    2. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain
    Search for more papers by this author
  • Vanesa López-González,

    1. Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    Search for more papers by this author
  • Birute Burnyte,

    1. Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
    Search for more papers by this author
  • Algirdas Utkus,

    1. Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
    Search for more papers by this author
  • Pablo Lapunzina,

    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    2. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain
    Search for more papers by this author
  • Victor L. Ruiz-Perez

    Corresponding author
    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    2. Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain
    • Correspondence to:

      Victor L. Ruiz-Perez, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain.

      E-mail: vlruiz@iib.uam.es

      Correspondence to:

      Encarna Guillén-Navarro; Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia, Spain.

      E-mail: guillen.encarna@gmail.com

    Search for more papers by this author

  • Conflict of interest: none.

Abstract

The IFITM5 gene has recently been found to be mutated in patients with autosomal dominant osteogenesis imperfecta (OI) type V. This form of OI is characterized by distinctive clinical manifestations, including hyperplastic callus formation at the site of fractures, calcification of the interosseous membrane of the forearm, and dislocation of the head of the radius. Notably, in spite of the fact that a considerable number of patients with IFITM5 mutations have been identified, to date all of them have been shown to have the same heterozygous mutation (c.-14C>T). Herein, we describe one patient with a de novo c.119C>T heterozygous mutation in IFITM5, which predicts p.Ser40Leu, and another with the recurrent c.-14C>T transition that was also apparently de novo. While the patient with the p.Ser40Leu mutation had none of the typical signs of OI type V and was diagnosed with limb shortening at prenatal stages, the patient with the c.-14C>T mutation developed hyperplastic calluses and had calcification of the forearm interosseous membrane. This study challenges the lack of allelic and clinical heterogeneity in IFITM5 mutations. © 2014 Wiley Periodicals, Inc.

Ancillary