Ten novel mutations in VMD2 associated with Best macular dystrophy (BMD)

Hum Mutat. 2003 Nov;22(5):418. doi: 10.1002/humu.9189.


Mutations in the vitelliform macular dystrophy 2 (VMD2) gene encoding besrtophin are responsible for Best macular dystrophy (BMD), a juvenile-onset autosomal dominant disorder of the central retina. Here, we report ten novel VMD2 mutations identified in clinically diagnosed BMD patients. The heterozygous alterations include nine missense mutations (c.32A>T, c.76G>C, c.85T>C, c.122T>C, c.122T>C, c.310G>C, c.722C>A, c.880C>G, c.893T>C) resulting in amino acid changes (respectively: Asn11Ile, Gly26Arg, Tyr29His, Leu41Pro, Trp102Arg, Asp104His, Thr241Asn, Leu294Val and Phe298Ser) located within four previously defined hotspot regions of the gene. In addition, a silent exonic mutation (c.624G>A) was identified in a two generation BMD pedigree. To determine a possible pathogenic effect of this variant, the consequences on splicing behaviour and potential exonic splice enhancer (ESE) motifs were analyzed. Finally, a 1-bp deletion (c.779delC) resulting in a frameshift mutation (Pro260fsX288) was found in exon 7, representing the first case of a potential frameshift mutation that affects the N-terminal half of the VMD2 protein. Besides a dominant negative effect which is likely attributable to the identified missense mutations, the deletion mutation suggests haploinsufficiency as an infrequent disease-causing mechanism in BMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bestrophins
  • Chloride Channels
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Genetic Variation
  • Humans
  • Macular Degeneration / genetics*
  • Mutation*
  • Polymorphism, Genetic
  • RNA Splicing


  • BEST1 protein, human
  • Bestrophins
  • Chloride Channels
  • Eye Proteins