A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies

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Demirhan O. , TURKMEN S., SCHWABE G., SOYUPAK S. , AKGUL E. , TASTEMIR D., ...Daha Fazla

JOURNAL OF MEDICAL GENETICS, cilt.42, ss.314-317, 2005 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 42 Konu: 4
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1136/jmg.2004.023564
  • Sayfa Sayıları: ss.314-317


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.