title: Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies.
abstract: Bone morphogenetic protein (BMP) signaling regulates a range of cellular processes and plays an important role in the specification and patterning of the early embryo. However, due to the functional redundancy of BMP ligands and receptors in tissues where they are coexpressed, relatively little is known about the role of individual BMP ligands in human disease. Here we report heterozygous variations in BMP7, including a frameshift, missense, and Kozak sequence mutation, in individuals with developmental eye anomalies and a range of systemic abnormalities, including developmental delay, deafness, scoliosis, and cleft palate. We determined that BMP7 is expressed in the developing eye, brain, and ear in human embryos in a manner consistent with the phenotype seen in our mutation cases. These data establish BMP7 as an important gene in human eye development, and suggest that BMP7 should be considered during clinical evaluation of individuals with developmental eye anomalies.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford, United Kingdom.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wyatt
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Osborne
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Ragge
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities / Q000378:metabolism; D001921:Brain / Q000002:abnormalities / Q000378:metabolism; D000013:Congenital Abnormalities / Q000235:genetics*; D004252:DNA Mutational Analysis; D004423:Ear / Q000002:abnormalities; D004427:Ear Diseases / Q000235:genetics; D005124:Eye Abnormalities / Q000235:genetics; D020022:Genetic Predisposition to Disease; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009154:Mutation; D010159:Palate / Q000002:abnormalities / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7