TY - JOUR
T1 - A homozygous frameshift mutation in BEST1 causes the classical form of best disease in an autosomal recessive mode
AU - Bitner, Hanna
AU - Mizrahi-Meissonnier, Liliana
AU - Griefner, Gabriel
AU - Erdinest, Inbar
AU - Sharon, Dror
AU - Banin, Eyal
PY - 2011/7
Y1 - 2011/7
N2 - Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode. METHODS. Clinical evaluation included detailed family history, a full ophthalmologic examination, electro-oculography (EOG), electroretinography, color vision testing, and ocular imaging. Mutation analysis was performed by direct sequencing of PCR products. RESULTS. Two young siblings affected by Best disease, as confirmed by funduscopy, retinal imaging, and electrophysiologic assessment, were recruited for the study. Molecular analysis revealed a novel homozygous deletion (c.1415delT) in the BEST1 gene leading to a frameshift followed by a premature stop codon, which cosegregated with the disease in a recessive mode. The heterozygous parents had normal visual acuity, retinal appearance, and function. The two heterozygous grandmothers, ages 61 and 62, also had normal Arden ratios on EOG, but one of them manifested moderate-to-severe dry non-neovascular age-related macular degeneration. CONCLUSIONS. We show here that the typical vitelliform phenotype of Best disease, usually transmitted in an autosomal dominant fashion, can be inherited as an autosomal recessive disease due to homozygosity for a frameshift mutation.
AB - Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode. METHODS. Clinical evaluation included detailed family history, a full ophthalmologic examination, electro-oculography (EOG), electroretinography, color vision testing, and ocular imaging. Mutation analysis was performed by direct sequencing of PCR products. RESULTS. Two young siblings affected by Best disease, as confirmed by funduscopy, retinal imaging, and electrophysiologic assessment, were recruited for the study. Molecular analysis revealed a novel homozygous deletion (c.1415delT) in the BEST1 gene leading to a frameshift followed by a premature stop codon, which cosegregated with the disease in a recessive mode. The heterozygous parents had normal visual acuity, retinal appearance, and function. The two heterozygous grandmothers, ages 61 and 62, also had normal Arden ratios on EOG, but one of them manifested moderate-to-severe dry non-neovascular age-related macular degeneration. CONCLUSIONS. We show here that the typical vitelliform phenotype of Best disease, usually transmitted in an autosomal dominant fashion, can be inherited as an autosomal recessive disease due to homozygosity for a frameshift mutation.
UR - http://www.scopus.com/inward/record.url?scp=80052924653&partnerID=8YFLogxK
U2 - 10.1167/iovs.11-7174
DO - 10.1167/iovs.11-7174
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C2 - 21467170
AN - SCOPUS:80052924653
SN - 0146-0404
VL - 52
SP - 5332
EP - 5338
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 8
ER -