ZFIN ID: ZDB-PUB-091113-6
GDF6, a novel locus for a spectrum of ocular developmental anomalies
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.
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.
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.