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A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies
  1. O Demirhan1,*,
  2. S Türkmen2,*,
  3. G C Schwabe3,
  4. S Soyupak4,
  5. E Akgül4,
  6. D Taştemir1,
  7. D Karahan1,
  8. S Mundlos2,3,
  9. K Lehmann2
  1. 1Department of Medical Biology and Genetics, Çukurova University, Adana, Turkey
  2. 2Institute for Medical Genetics, Charité, Berlin, Germany
  3. 3Max Planck Institute for Molecular Genetics, Berlin, Germany
  4. 4Department of Radiology, Çukurova University, Adana, Turkey
  1. Correspondence to:
 Stefan Mundlos
 Institut für Medizinische Genetik, Universitätsmedizin Berlin, Charité, Augustenburger Platz 1, 13353 Berlin, Germany;


We present a patient with acromesomelic chondrodysplasia and genital anomalies caused by a novel homozygous mutation in BMPR1B, the gene coding for bone morphogenetic protein receptor 1B. The 16 year old girl, the offspring of a multiconsanguinous family, showed a severe form of limb malformation consisting of aplasia of the fibula, severe brachydactyly, ulnar deviation of the hands, and fusion of carpal/tarsal bones. In addition, she presented with hypoplasia of the uterus and ovarian dysfunction resulting in hypergonadotrophic hypogonadism. Mutation analysis of BMPR1B revealed a homozygous 8 bp deletion (del359–366). This mutation is expected to result in a loss of function and is thus different from the heterozygous missense mutations in BMPR1B recently shown to cause brachydactyly type A2 through a dominant negative effect. The patient’s skeletal phenotype shows an overlap with the clinical spectrum of the acromesomelic chondrodysplasias of the Grebe, Hunter-Thompson, and DuPan types caused by homozygous mutations in the gene coding for growth differentiation factor 5 (GDF5) which is a high-affinity ligand to BMPR1B. However, the phenotype described here differs from GDF5 associated chondrodysplasias because of the additional presence of genital anomalies and the distinct limb phenotype.

  • BDA2, brachydactyly A2
  • BDC, brachydactyly type C
  • BMP, bone morphogenetic protein
  • BMPR, bone morphogenetic protein receptor
  • bp mouse, brachypodism mouse
  • FSH, follicle stimulating hormone
  • GDF5, growth differentiation factor 5
  • LH, luteinising hormone
  • MCPP, metacarpophalangeal profile
  • TGF-β, transforming growth factor-β
  • acromesomelic chondrodysplasia
  • bone morphogenetic protein receptor
  • GDF5
  • genital malformation
  • ovarian dysfunction

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  • * Both authors contributed equally to this work.

  • Competing interests: none declared