GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2007 Jan 20

PMID 17236135

Citations 56

Authors

Mika Asai-Coakwell

Curtis R French

Karyn M Berry

Ming Ye

Ron Koss

Martin Somerville

Rosemary Mueller

Veronica Van Heyningen

Andrew J Waskiewicz

Ordan J Lehmann

Affiliations

Soon will be listed here.

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.

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