A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis

Am J Hum Genet. 2009 Feb;84(2):274-8. doi: 10.1016/j.ajhg.2009.01.007. Epub 2009 Feb 5.


Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T-->G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS Proteins
  • Base Sequence
  • Consanguinity
  • Ectopia Lentis / genetics*
  • Female
  • Genes, Recessive*
  • Genetic Markers
  • Homozygote
  • Humans
  • Jordan
  • Lod Score
  • Male
  • Mutation*
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Siblings
  • Thrombospondins / genetics*


  • ADAMTSL4 protein, human
  • Genetic Markers
  • Thrombospondins
  • ADAMTS Proteins