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.
The gene encoding ROM1, a photoreceptor-specific membrane protein, has been independently mapped within the Best's disease region and has thus become a strong candidate for the Best's disease gene.
To describe the presenting features and functional outcomes in a series of patients with choroidal neovascular membrane complicating BEST1-related retinopathy (Best disease and autosomal recessive bestrophinopathy).
The majority of disease-associated mutations in <i>BEST1</i> constitute missense mutations and were shown <i>in vitro</i> to lead to a reduction in mutant protein half-life causing Best disease (BD), a rare autosomal dominant macular dystrophy.
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.
In three of five family members, the sequence analysis of the BEST1 gene revealed a single Phe-to-Leu transition at nucleotide 305 associated with clinical evidence of Best disease.
Compared to baseline, BMD significantly increased for S-WEIGHT in the arms (+4%, P<0.001), legs (+8%, P<0.01), pelvis (+6%, P<0.01) and lumbar spine (+4%, P<0.05), whereas BMD did not significantly change for S-CORE at any site.
Five patients (10 eyes) with uniocular manifestation of BEST1 mutation causing Best disease were ascertained retrospectively from the clinical and genetic databases.
Further, the inheritance pattern of BEST1 mutations in the families confirmed the diagnosis of ARB in probands in families A, B and C, while the inheritance of heterozygous BEST1 mutation in family D (p.Thr91Ile) was suggestive of BVMD.
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.
Best's macular dystrophy (BMD), also known as vitelliform macular degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration with mainly juvenile onset.