Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations.
OBJECTIVE
(1) To evaluate the spectrum of BEST1 mutations within Australian Best Disease or vitelliform macular dystrophy (VMD) pedigrees, including any novel mutations; (2) to analyse the range of clinical presentations of this cohort; (3) to determine any possible genotype-phenotype correlations and (4) to compare clinical data of patients with phenotypic VMD, both with and without a BEST1 mutation.


METHODS
Patients with suspected VMD were referred to clinical centres for ophthalmological assessment and genetic screening. When a mutation was identified in a proband, further family members were invited for clinical and genetic screening.


RESULTS
We identified 42 patients with one of 13 BEST1 mutations. Seven mutations were novel. There were a further 14 probands in whom a BEST1 mutation was not identified. Median visual acuity in both VMD (mutation positive) and clinical VMD (no BEST1 mutation identified) groups reached driving standards (6/12 or better).


CONCLUSIONS
We did not identify any firm genotype-phenotype correlations in our Australian VMD pedigrees, in which there was a spectrum of BEST1 mutations and marked variation in clinical presentation. Genetic screening remains the gold standard for VMD diagnosis. Patients should be counselled that visual acuity might remain at or above driving standards in at least one eye even in the presence of a BEST1 mutation.
Department of Ophthalmology Melbourne, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
A C
AC
Cohn
C
C
Turnbull
J B
JB
Ruddle
R H
RH
Guymer
L S
LS
Kearns
S
S
Staffieri
H T
HT
Daggett
A W
AW
Hewitt
D A
DA
Mackey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D003118:Color Perception / Q000502:physiology; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000473:pathology; D014792:Visual Acuity; D014794:Visual Fields / Q000502:physiology; D057826:Vitelliform Macular Dystrophy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins