Best Disease: Global Mutations Review, Genotype–Phenotype Correlation, and Prevalence Analysis in the Israeli Population

Avigail Beryozkin, Ifat Sher, Miriam Ehrenberg, Dinah Zur, Hadas Newman, Libe Gradstein, Francis Simaan, Ygal Rotenstreich, Nitza Goldenberg-Cohen, Irit Bahar, Anat Blumenfeld, Antonio Rivera, Boris Rosin, Iris Deitch-Harel, Ido Perlman, Hadas Mechoulam, Itay Chowers, Rina Leibu, Tamar Ben-Yosef, Eran PrasEyal Banin, Dror Sharon, Samer Khateb

    Research output: Contribution to journalReview articlepeer-review


    PURPOSE. To review all reported disease-causing mutations in BEST1, perform genotype–phenotype correlation, and estimate disease prevalence in the Israeli population. METHODS. Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. RESULTS. A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. CONCLUSIONS. This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

    Original languageEnglish
    Article number39
    JournalInvestigative Ophthalmology and Visual Science
    Issue number2
    StatePublished - 1 Feb 2024


    • BEST1
    • genotype-phenotype correlation
    • macular degeneration
    • mutations review
    • prevalence

    ASJC Scopus subject areas

    • Sensory Systems
    • Cellular and Molecular Neuroscience
    • Ophthalmology


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