title: Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis.
abstract: Coats' disease is characterized by abnormal retinal vascular development (so-called 'retinal telangiectasis') which results in massive intraretinal and subretinal lipid accumulation (exudative retinal detachment). The classical form of Coats' disease is almost invariably isolated, unilateral and seen in males. A female with a unilateral variant of Coats' disease gave birth to a son affected by Norrie disease. Both carried a missense mutation within the NDP gene on chromosome Xp11.2. Subsequently analysis of the retinas of nine enucleated eyes from males with Coats' disease demonstrated in one a somatic mutation in the NDP gene which was not present within non-retinal tissue. We suggest that Coats' telangiectasis is secondary to somatic mutation in the NDP gene which results in a deficiency of norrin (the protein product of the NDP gene) within the developing retina. This supports recent observations that the protein is critical for normal retinal vasculogenesis.
authors.affiliation: University Department of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester M13 OJH, UK. gblack@fs1.cmht.nwest.nhs.uk
authors.forename: G C
authors.initials: GC
authors.lastname: Black
authors.forename: R
authors.initials: R
authors.lastname: Perveen
authors.forename: R
authors.initials: R
authors.lastname: Bonshek
authors.forename: M
authors.initials: M
authors.lastname: Cahill
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: I C
authors.initials: IC
authors.lastname: Lloyd
authors.forename: D
authors.initials: D
authors.lastname: McLeod
mesh_terms: D019943:Amino Acid Substitution; D001766:Blindness / Q000151:congenital / Q000235:genetics*; D002648:Child; D004303:Dosage Compensation, Genetic; D015353:Eye Enucleation; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D020180:Heteroduplex Analysis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D020125:Mutation, Missense; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012160:Retina / Q000254:growth & development*; D012163:Retinal Detachment / Q000235:genetics; D012164:Retinal Diseases / Q000235:genetics*; D015792:Retinal Dysplasia / Q000235:genetics*; D012171:Retinal Vessels / Q000254:growth & development* / Q000473:pathology; D013577:Syndrome; D013684:Telangiectasis / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins