title: Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and primary open-angle glaucoma co-segregating in a family.
abstract: OBJECTIVE
  To describe an Australian pedigree of European descent with a variable autosomal dominant phenotype of: pediatric cortical cataract (CC), asymmetric myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and primary open-angle glaucoma (POAG).
  
  
  METHODS
  Probands with CC, FEVR, and POAG were enrolled in three independent genetic eye studies in Tasmania. Genealogy confirmed these individuals were closely related and subsequent examination revealed 11 other family members with some or all of the associated disorders.
  
  
  RESULTS
  Twelve individuals had CC thought to be of childhood onset, with one child demonstrating progressive lenticular opacification. One individual had severe retinal detachment while five others had dragged retinal vessels. Seven individuals had POAG. Seven individuals had myopia in at least one eye ≤-3 Diopters. DNA testing excluded mutations in myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein receptor-related protein 5 (LRP5), but only partly excluded EVR3. Multipoint linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms (SNPs) of interest, but no statistically significant focal localization.
  
  
  CONCLUSIONS
  This unusual clustering of ophthalmic diseases suggests a possible single genetic cause for an apparently new cataract syndrome. This family's clinical ocular features may reflect the interplay between retinal disease with lenticular changes and axial length in the development of myopia and glaucoma.
authors.affiliation: Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia. D.Mackey@utas.edu.au
authors.forename: D A
authors.initials: DA
authors.lastname: Mackey
authors.forename: A W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: J B
authors.initials: JB
authors.lastname: Ruddle
authors.forename: B
authors.initials: B
authors.lastname: Vote
authors.forename: R G
authors.initials: RG
authors.lastname: Buttery
authors.forename: C
authors.initials: C
authors.lastname: Toomes
authors.forename: R
authors.initials: R
authors.lastname: Metlapally
authors.forename: Y J
authors.initials: YJ
authors.lastname: Li
authors.forename: K N
authors.initials: KN
authors.lastname: Tran-Viet
authors.forename: F
authors.initials: F
authors.lastname: Malecaze
authors.forename: P
authors.initials: P
authors.lastname: Calvas
authors.forename: T
authors.initials: T
authors.lastname: Rosenberg
authors.forename: J A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: T L
authors.initials: TL
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001251:Astigmatism / Q000150:complications / Q000235:genetics*; D002386:Cataract / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005123:Eye / Q000473:pathology / Q000503:physiopathology*; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000150:complications / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009216:Myopia / Q000150:complications / Q000235:genetics*; D010024:Osteoporosis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013648:Tasmania; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000235:genetics*; D044465:White People / Q000235:genetics*