title: Grebe dysplasia and the spectrum of CDMP1 mutations.
abstract: We report on a 4-year-old boy with the typical phenotype of Grebe dysplasia born to consanguineous parents. The father seems to be unaffected; the mother presents with brachydactyly type C (BdC). PCR amplification and sequencing of the cartilage-derived morphogenetic protein 1 (CDMP1) gene of the parents led to the identification of a heterozygous insertion of a single G at nucleotide 206. The mutation that causes frameshift and premature termination is predicted to result in functional haploinsufficiency. The child is homozygous for the insertion (insG206). The phenotypic spectrum of this loss-of-function mutation ranges from normal or BdC in heterozygotes to Grebe-type chondrodysplasia in the homozygously affected and seems to be due to CDMP1 gradient effects during pattern formation. A dominant negative action on other bone morphogenetic proteins is unlikely to cause the severe disruption of skeletogenesis seen in this case of Grebe dysplasia.
authors.affiliation: Children's Hospital, University of Mainz, Langenbeckstr. 1, D-55101 Mainz, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Stelzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Winterpacht
authors.forename: Jürgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zabel
mesh_terms: D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense; D018076:DNA, Complementary / Q000032:analysis; D016368:Frameshift Mutation; D055428:Growth Differentiation Factor 5; D006801:Humans; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011859:Radiography
chemical_list: D019485:Bone Morphogenetic Proteins; D018389:Codon, Nonsense; D018076:DNA, Complementary; D055428:Growth Differentiation Factor 5