Five patients (10 eyes) with uniocular manifestation of BEST1 mutation causing Best disease were ascertained retrospectively from the clinical and genetic databases.
Two previously unreported disease-associated variants in the BEST1 gene (p.Gly15Arg and p.Arg105Gly) were found in Slovenian patients with Best disease.
We describe the atypical phenotype and high intrafamilial variability associated with a new mutation in the BEST1 gene in an Italian family affected with Best vitelliform macular dystrophy.
Clinical presentations of angle closure glaucoma and/or focal choroidal excavation may be related to BVMD, underlining the necessity of multimodal studies and risk assessment of angle closure glaucoma in BEST1 mutation carriers.
Although BEST1 gene mutations and polymorphisms have previously been reported in various ethnic groups, the current study identified, for the first time to the best of our knowledge, two novel BEST1 gene mutations in patients with BVMD.
Using adenovirus-mediated gene transfer, we overexpressed Best1 and the BVMD mutant Best1W93C in fhRPE cells and assessed resting transepithelial potential (TEP), transepithelial resistance, short circuit current (Isc), and intracellular Ca2+ levels.
Patients affected by the subclinical form of Best vitelliform macular dystrophy (positive testing for BEST1 gene mutation, fully preserved best-corrected visual acuity, normal fundus appearance) were recruited.
The database of a national referral center specialized in genetic sensory diseases was screened for patients with a macular vitelliform dystrophy without identified mutation or small deletion or large rearrangement in BEST1 and PRPH2 genes.Forty-nine families were included.
The overall carrier frequency for BMD mothers was significantly higher than for DMD (89.5% vs 57.6%, P<0.05), probably as BMD patients can leave descendants.
Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the oligomerization, of Bestrophin-1.
Prospective, observational case series.Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee.
Furthermore, MDCK cells can substitute for RPE when examining the effects of BVMD causing mutations on Best1 localization if co-expressed with WT Best1.
In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene.
Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level.
The high prevalence of novel variants and the frequent report of a specific variant (p.Arg25Trp) that has rarely been described in other ethnic groups suggests a distribution of BEST1 variants peculiar to Italian VMD patients.
Four family members with the c.253T>C p.Y85H mutation in the BEST1 gene and BVMD in different stages also exhibited anterior segment abnormalities such as shallow anterior chambers (two cases), and reduced axial lengths in all cases.
As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy.
Six subjects were identified with BEST1 mutations (three male, three female; aged 8 to 30 years) without clinically detectable (subclinical) Best VMD (absence of both symptoms and funduscopic lesions).