Jan 15, 2014

Mutation of SALL2 causes recessive ocular coloboma in humans and mice

Human Molecular Genetics
Daniel KelbermanJane C Sowden

Abstract

Ocular coloboma is a congenital defect resulting from failure of normal closure of the optic fissure during embryonic eye development. This birth defect causes childhood blindness worldwide, yet the genetic etiology is poorly understood. Here, we identified a novel homozygous mutation in the SALL2 gene in members of a consanguineous family affected with non-syndromic ocular coloboma variably affecting the iris and retina. This mutation, c.85G>T, introduces a premature termination codon (p.Glu29*) predicted to truncate the SALL2 protein so that it lacks three clusters of zinc-finger motifs that are essential for DNA-binding activity. This discovery identifies SALL2 as the third member of the Drosophila homeotic Spalt-like family of developmental transcription factor genes implicated in human disease. SALL2 is expressed in the developing human retina at the time of, and subsequent to, optic fissure closure. Analysis of Sall2-deficient mouse embryos revealed delayed apposition of the optic fissure margins and the persistence of an anterior retinal coloboma phenotype after birth. Sall2-deficient embryos displayed correct posterior closure toward the optic nerve head, and upon contact of the fissure margins, dissolution of the basal...Continue Reading

  • References68
  • Citations15

References

  • References68
  • Citations15

Citations

Mentioned in this Paper

Embryo
Angle Closure Glaucoma
HEK293 Cells
Mutation, Nonsense
Fissure
Eye Morphogenesis
Entire Retina
salm
Bulla
Fundus Coloboma

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