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

J Med Genet. 2005 Apr;42(4):314-7. doi: 10.1136/jmg.2004.023564.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Bone Morphogenetic Protein Receptors, Type I / genetics*
  • Bone Morphogenetic Proteins / genetics
  • Female
  • Growth Differentiation Factor 5
  • Homozygote*
  • Humans
  • Limb Deformities, Congenital / genetics*
  • Models, Genetic
  • Mutation*
  • Ovarian Diseases / genetics*
  • Pedigree
  • Phenotype
  • Sequence Analysis

Substances

  • Bone Morphogenetic Proteins
  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • BMPR1B protein, human
  • Bone Morphogenetic Protein Receptors, Type I