title: A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies.
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.
authors.affiliation: Department of Medical Biology and Genetics, Cukurova University, Adana, Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Demirhan
authors.forename: S
authors.initials: S
authors.lastname: Türkmen
authors.forename: G C
authors.initials: GC
authors.lastname: Schwabe
authors.forename: S
authors.initials: S
authors.lastname: Soyupak
authors.forename: E
authors.initials: E
authors.lastname: Akgül
authors.forename: D
authors.initials: D
authors.lastname: Tastemir
authors.forename: D
authors.initials: D
authors.lastname: Karahan
authors.forename: S
authors.initials: S
authors.lastname: Mundlos
authors.forename: K
authors.initials: K
authors.lastname: Lehmann
mesh_terms: D000293:Adolescent; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D005260:Female; D055428:Growth Differentiation Factor 5; D006720:Homozygote; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D010049:Ovarian Diseases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017421:Sequence Analysis
chemical_list: D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I