title: A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis.
abstract: 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.
authors.affiliation: Shafallah Medical Genetics Center, Doha, Qatar.
authors.forename: Dina
authors.initials: D
authors.lastname: Ahram
authors.forename: T Shawn
authors.initials: TS
authors.lastname: Sato
authors.forename: Abdulghani
authors.initials: A
authors.lastname: Kohilan
authors.forename: Marwan
authors.initials: M
authors.lastname: Tayeh
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Leal
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Salem
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
mesh_terms: D000071096:ADAMTS Proteins; D001483:Base Sequence; D003241:Consanguinity; D004479:Ectopia Lentis / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007597:Jordan; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D019699:Thrombospondins / Q000235:genetics*
chemical_list: C486779:ADAMTSL4 protein, human; D005819:Genetic Markers; D019699:Thrombospondins; D000071096:ADAMTS Proteins