title: Pseudo-vitelliform macular detachment and cuticular drusen: exclusion of 6 candidate genes.
abstract: OBJECTIVE
  The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes.
  
  
  METHODS
  Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing.
  
  
  RESULTS
  All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population.
  
  
  CONCLUSIONS
  Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York 10032, USA.
authors.forename: Irene A
authors.initials: IA
authors.lastname: Barbazetto
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Yannuzzi
authors.forename: Christina M
authors.initials: CM
authors.lastname: Klais
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Merriam
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.forename: Enrico
authors.initials: E
authors.lastname: Peiretti
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Yannuzzi
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008266:Macula Lutea / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012163:Retinal Detachment / Q000235:genetics*; D015593:Retinal Drusen / Q000235:genetics*