■回顾所有报告的BEST1致病突变,进行基因型-表型相关性,并估计以色列人口中的疾病患病率。
■收集了过去20年来来自9个以色列医疗中心的被诊断为最佳疾病和相关疾病的患者的医疗记录,包括眼部发现在内的临床数据,电生理学结果,和视网膜成像。突变检测主要涉及全外显子组测序和候选基因分析。人口数据来自以色列统计局(2023年1月)。还进行了文献计量研究以从在线来源收集突变数据。
■共有134名患者被临床诊断为最佳疾病和相关状况。据估计,最佳疾病的患病率为127,000人中的1人,阿拉伯穆斯林(76,000人中的1人)比犹太人(145,000人中的1人)高。在76个人(57%)中确定了遗传原因,主要表现为由BEST1突变引起的常染色体显性遗传(58例)。关键保守结构域被鉴定为由高百分比的显性错义突变组成,主要在BEST1蛋白的跨膜结构域和胞内区域(Ca2+结合结构域)。
■这项研究代表了以色列和全球报告的最大的最佳疾病患者队列。以色列的患病率类似于丹麦,但低于美国。BEST1蛋白内的关键保守结构域是正常功能的关键,即使是这些领域的轻微错觉改变也会导致主要的疾病表现。由于疾病的临床表现多变,基因检测作为最佳疾病诊断的金标准是必不可少的。
UNASSIGNED: To
review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.