A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies. Issue 4 (1st April 2005)

• Record Type: Journal Article
• Authors: Demirhan, O; Türkmen, S; Schwabe, G C; Soyupak, S; Akgül, E; Taştemir, D; Karahan, D; Mundlos, S; Lehmann, K
• Is Part Of: Journal of medical genetics. Volume 42:Issue 4(2005)
• Page Start: 314
• Page End: 317
• Publication Date: 2005-04-01
• Subjects: 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; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2004.023564
• Languages: English
• ISSNs: 1468-6244

Abstract

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.