title: Clinical evaluation of 3 families with basal laminar drusen caused by novel mutations in the complement factor H gene.
abstract: OBJECTIVE
  To identify novel complement factor H (CFH) gene mutations and to specify the clinical characteristics in patients with basal laminar drusen (BLD), a clinical subtype of age-related macular degeneration.
  
  
  METHODS
  Twenty-one probands with BLD were included in this study. The ophthalmic examination included nonstereoscopic 30° color fundus photography, fluorescein angiography, and high-resolution spectral-domain optical coherence tomography. Renal function was tested by measurement of serum creatinine and urea nitrogen levels. Venous blood samples were drawn for genomic DNA, and all coding exons and splice junctions of the CFH gene were analyzed by direct sequencing.
  
  
  RESULTS
  In 3 families, we identified novel heterozygous mutations in theCFHgene: p.Ile184fsX, p.Lys204fsX, and c.1697-17_-8del. Ten of 13 mutation carriers displayed the BLD phenotype with a wide variety in clinical presentation, ranging from limited macular drusen to extensive drusen in the posterior pole as well as the peripheral retina. Two patients with BLD developed endstage kidney disease as a result of membranoproliferative glomerulonephritis type II.
  
  
  CONCLUSIONS
  The early-onset BLD phenotype can be caused by heterozygous mutations in the CFH gene. Because some patients with BLD are at risk to develop membranoproliferative glomerulonephritis type II, we recommend that patients with extensive BLD undergo screening for renal dysfunction.
  
  
  CONCLUSIONS
  Elucidation of the clinical BLD phenotype will facilitate identification of individuals predisposed to developing disease-related comorbidity, such as membranoproliferative glomerulonephritis type II. Moreover, with upcoming treatment modalities targeting specific components of the complement system, early identification of patients with BLD and detection of the genetic defect become increasingly important.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Philips van Leydenlaan, 6525 EX Nijmegen, the Netherlands. j.vandeven@ohk.umcn.nl
authors.forename: Johannes P H
authors.initials: JP
authors.lastname: van de Ven
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: Sacha
authors.initials: S
authors.lastname: Fauser
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Dzenita
authors.initials: D
authors.lastname: Smailhodzic
authors.forename: Frederieke
authors.initials: F
authors.lastname: Schoenmaker-Koller
authors.forename: Jeroen
authors.initials: J
authors.lastname: Klevering
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005451:Fluorescein Angiography; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015593:Retinal Drusen / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H