title: A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae.
abstract: OBJECTIVE
  To examine the ocular malformations and identify the molecular genetic basis for autosomal recessive ectopia lentis et pupillae in five Norwegian families.
  
  
  METHODS
  Ten affected persons and 11 first-degree relatives of five Norwegian families underwent ophthalmic and general medical examination. Molecular genetic studies included homozygosity mapping with SNP markers, DNA sequencing, and RT-PCR analysis.
  
  
  RESULTS
  Ocular signs in affected persons were increased median corneal thickness and astigmatism, angle malformation with prominent iris processes, displacement of the pupil and lens, lens coloboma, spherophakia, loss of zonular threads, early cataract development, glaucoma, and retinal detachment. No cardiac or metabolic abnormalities known to be associated with ectopia lentis were detected. Affected persons shared a 0.67 cM region of homozygosity on chromosome 1. DNA sequencing revealed a novel mutation in ADAMTSL4, c.767_786del20. This deletion of 20 base pairs (bp) results in a frameshift and an introduction of a stop codon 113 bp downstream, predicting a C-terminal truncation of the ADAMTSL4 protein (p.Gln256ProfsX38). Expression of truncated ADAMTSL4 mRNA was confirmed by RT-PCR analysis. Three of 190 local blood donors were carriers of this mutation.
  
  
  CONCLUSIONS
  Ectopia lentis et pupillae is associated with a number of malformations primarily in the anterior segment of the eye. The causative mutation, which is the first to be described in ectopia lentis et pupillae, disrupts the same gene function previously shown to cause isolated ectopia lentis. The mutation is ancient and may, therefore, be spread to a much larger population than the investigated one.
authors: Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway.
authors: Anne E
authors: AE
authors: Christensen
authors: Torunn
authors: T
authors: Fiskerstrand
authors: Per M
authors: PM
authors: Knappskog
authors: Helge
authors: H
authors: Boman
authors: Eyvind
authors: E
authors: Rødahl
mesh_terms: D000071096:ADAMTS Proteins; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011681:Pupil Disorders / Q000175:diagnosis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019699:Thrombospondins / Q000235:genetics*
chemical_list: C486779:ADAMTSL4 protein, human; D012333:RNA, Messenger; D019699:Thrombospondins; D000071096:ADAMTS Proteins