What Is Known About The Genetic Causes Of Vitelliform Macular Dystrophy?
Human molecular geneticists have determined that VMD is inherited in an autosomal dominant manner and is caused by one or mutations in either one of two genes, which are designated BEST1 and PRPH2. Specifically, mutation in either one of a person's two BEST1 genes is causative of Best disease and, in limited cases, adult-onset VMD. Mutation in either copy of a person's PRPH2 gene causes the adult-onset form of VMD.
The BEST1 gene encodes a protein known as bestrophin. Bestrophin molecules form chloride channels in cells of the macula, which are needed to move chloride ions into and out of these cells. Those who have a mutated copy of BEST1 either make a reduced amount of bestrophin or make a defective variant of bestrophin. In either case, they do not sufficiently form enough functioning channels to control the movement of chloride ions into and out of retinal cells, which thereby causes these to ultimately malfunction.
The PRPH2 gene encodes the protein peripherin. Peripherin is needed to maintain the integrity of structures within cells of the macula that house light-sensitive pigments that are needed for sensing light. Those who cannot produce peripherin in sufficient quantity or who produce an aberrant form of peripherin are unable to maintain these structures, and therefore unable to store these light-sensitive pigments.
Interestingly, there are many documented cases in which individuals suffer from the adult-onset form of VMD but do not have a mutation in any copy of their BEST1 and PRPH2 genes. This finding has led medical professionals to speculate that a third, unknown gene also may be responsible for adult-onset VMD or that some cases of adult-onset VMD do not have a genetic cause. Further studies will be needed to determine if either or both of these hypotheses are true.
This article is only meant to provide some basic information regarding the genetic condition known as vitelliform macular dystrophy. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.