As a result of the preference for consanguineous/endogamous marriages, the Israeli Arab population is composed of isolated communities with relatively frequent autosomal recessive (AR) conditions in each community. Clinical diagnosis of affected individuals has uncovered the pathogenic variants throughout the years. We investigated the diversity of pathogenic AR variants in a single village in northern Israel by exome analysis of 50 random, healthy adults descendants of the founders. Only likely pathogenic and pathogenic variants in known AR genes were selected. In this study 48 AR variants were found, of which 12 had been previously diagnosed in patients from this village, and for 11 with a frequency compatible with the frequency already known. Among the other 36 variants, 12 had been previously diagnosed in affected individuals in other Arab communities in Israel and 24 variants had not been previously characterized in this population. Of the 35 variants associated with conditions of moderate–severe medical consequences, only eight were known previously in this village. These findings emphasize the importance to better delineate the conditions at risk in a defined community, in particular for the development of preventive measures such as screening tests for reproductive couples, and for genetic counseling.

中文翻译：

---

孤立社区中常染色体隐性变异的景观：对生殖目的人群筛查的意义

由于偏爱近亲/同婚婚姻，以色列阿拉伯人口由孤立的社区组成，每个社区都有相对频繁的常染色体隐性遗传 (AR) 条件。多年来，对受影响个体的临床诊断已经发现了致病变异。我们通过对 50 名随机健康成人后代的外显子组分析，调查了以色列北部一个村庄的致病性 AR 变异的多样性。仅选择已知 AR 基因中可能的致病和致病变异。在这项研究中，发现了 48 种 AR 变异，其中 12 种以前曾在该村的患者中被诊断过，其中 11 种的频率与已知频率兼容。在其他 36 个变种中，之前在以色列其他阿拉伯社区的受影响个体中已诊断出 12 种变异，而该人群中先前未对 24 种变异进行表征。在与中度至重度医疗后果相关的 35 种变体中，该村以前只有 8 种已知。这些发现强调了更好地描述特定社区的风险状况的重要性，特别是对于制定预防措施，例如生殖夫妇的筛查测试和遗传咨询。