Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations

Abstract

Purpose (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. Patients and 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). Conclusion 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.

Clinical and genetic heterogeneity in Slovenian patients with BEST disease

“…This protein is predicted to have four transmembrane domains (Marquardt et al 1998;Sohn et al 2009) and is localized to the basolateral plasma membrane of the RPE (Marquardt et al 1998;Petrukhin et al 1998), where it is assumed to act as a Ca 2+ -activated Cl À and HCO À 3 channel regulator of ion transport (Sun et al 2002;Qu & Hartzell 2008;Xiao et al 2010). It is well known that with the progression of the disease and a visual acuity of 0.2 or less, an evident shift of fixation to the preferential fixation locus can be observed by microperimetry (Jarc-Vidmar et al 2006;Querques et al 2009;Cohn et al 2011). Typical symptoms of BVMD include blurred vision, decrease in central vision or metamorphopsia.…”

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

“…In total, we identified 36 distinct disease-causing variants of the BEST1 gene in this cohort, which included missense (28/36, 77.8%), splicing effect (4/36, 11.1%), nonsense (3/36, 8.3%), and frameshift small duplication (1/ 36, 2.8%) mutations (Supplementary Table S3). [23][24][25][26][27][28] The RQ-PCR analysis revealed no large deletions or insertions of the BEST1 gene in eight patients.…”

Electrooculography and Optical Coherence Tomography Reveal Late-Onset Best Disease

“…1,2,6 On funduscopic examination, the classic BVMD lesion resembles a sunny side up egg. The previtelliform stage is characterized by only an abnormal EOG with no associated ocular findings.…”

“…1,6 In addition to dilated retinal evaluation, multiple diagnostic tests are used in the evaluation of patients suspected of having Best disease. Most AOFVD patients retain adequate near visual acuity throughout life.…”

“…1,2,6,7 Fundus autofluorescence and SD-OCT are contemporary diagnostic imaging technologies of value in the evaluation of patients with retinal disease. In cases of Best disease, the FA typically reveals hypofluorescence of the lesion owing to the blockage caused by lipofuscin accumulation within the RPE.…”