PUBLICATION

GDF6, a novel locus for a spectrum of ocular developmental anomalies

Authors
Asai-Coakwell, M., French, C.R., Berry, K.M., Ye, M., Koss, R., Somerville, M., Mueller, R., van Heyningen, V., Waskiewicz, A.J., and Lehmann, O.J.
ID
ZDB-PUB-091113-6
Date
2007
Source
American journal of human genetics   80(2): 306-315 (Journal)
Registered Authors
Lehmann, Ordan J., van Heyningen, Veronica, Waskiewicz, Andrew
Keywords
none
MeSH Terms
  • Animals
  • Bone Morphogenetic Proteins/genetics*
  • Bone Morphogenetic Proteins/metabolism
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 8/genetics
  • Coloboma/genetics*
  • Disease Models, Animal
  • Embryo, Nonmammalian/metabolism
  • Female
  • Genetic Predisposition to Disease*
  • Growth Differentiation Factor 6
  • Humans
  • Karyotyping
  • Male
  • Phenotype
  • Recombination, Genetic*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
17236135 Full text @ Am. J. Hum. Genet.
Abstract
Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband's phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping