title: Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract.
abstract: OBJECTIVE
  To genetically and phenotypically describe a new ADAM9 homozygous mutation in a consanguineous family from Egypt with autosomal recessive cone-rod dystrophy (arCRD), anterior polar and posterior subcapsular cataract.
  
  
  METHODS
  The parents and their six children were included. They underwent a complete ophthalmic examination with fundus photography and optical coherence tomography (OCT).
  
  
  METHODS
  DNA was extracted from peripheral blood from all family members. Screening for mutations in genes known to be implicated in retinal disorders was done with the IROme, an in-solution enrichment array, followed by high-throughput sequencing. Validation of the results was done by bidirectional Sanger sequencing of ADAM9 exon 14, including exon-intron junctions. Screening of normal controls was done by denaturing high-performance liquid chromatography.
  
  
  RESULTS
  arCRD was diagnosed in the mother and two of her children. Bilateral anterior polar and posterior subcapsular cataract was observed in the mother and bilateral dot cataract was diagnosed in three of the four children not affected with arCRD, one of whom also had glaucoma. The characteristics of the arCRD were childhood-onset visual impairment, reorganisation of the retinal pigment epithelium with mid-periphery greyish-white discolouration, attenuated retinal vasculatur and optic disc pallor. A coloboma-like macular lesion was observed in one of the arCRD-affected children. IROme analysis identified a c.1396-2A>G homozygous mutation in the splice acceptor site of intron 13 of ADAM9. This mutation was homozygous in the two children affected by arCRD and in their affected mother. This mutation was heterozygous in the unaffected father and the four unaffected children.
  
  
  CONCLUSIONS
  We identified a novel autosomal recessive ADAM9 mutation causing arCRD in a consanguineous Egyptian family. The percentage of arCRD cases caused by mutation in ADAM9 remains to be determined. Few families are reported in the literature to date; hence extensive clinical descriptions of families with ADAM9 mutations are of significant importance.
authors.affiliation: Department of Ophthalmology, Zagazig University, Zagazig, Egypt.
authors.forename: Wael M
authors.initials: WM
authors.lastname: El-Haig
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland Department of Ophthalmology, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jakobsson
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Favez
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland Department of Ophthalmology, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland EPFL-Faculté des Sciences du Vivant, Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland Department of Ophthalmology, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland.
authors.forename: Hana
authors.initials: H
authors.lastname: Abouzeid
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004534:Egypt; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D022821:RNA Splice Sites; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D022821:RNA Splice Sites; D051722:ADAM Proteins; C098339:ADAM9 protein, human
keywords: Dystrophy; Genetics; Retina; Vision