Consanguinity, commonplace in many regions around the globe, is associated with an increased risk of autosomal recessive (AR) genetic disorders. Consequently, consanguineous couples undergoing preimplantation genetic diagnosis (PGD) for one Mendelian disorder may be at increased risk for a child with a second, unrelated AR genetic disorder. We examined the yield of exome analysis for carrier screening of additional AR disorders, beyond the primary diagnosis, amongst consanguineous vs. non-consanguineous populations. Parental samples from trio exomes of 102 consanguineous families and 105 non-consanguineous controls were evaluated for shared carrier status, after disregarding the primary molecular diagnosis. Results were sub-classified according to disease severity. Secondary shared carrier status for pathogenic and likely pathogenic variants leading to AR disorders of moderate to profound severity was identified in 10/102 (9.8%) consanguineous couples, as compared to 1/105 (0.95%) non-consanguineous couples (χ² = 8.0565, p value < 0.005). Higher inbreeding coefficient values, calculated from individual exomes, correlated with secondary shared carrier status for diseases of moderate to profound severity (r = 0.17, p value < 0.0125). Our results indicate that consanguineous couples undergoing PGD are at increased risk for a second genetic disease of moderate to profound severity. This study represents an underestimate of the rate of secondary shared carrier status due to inability to detect deep intronic variants, no assessment of copy number variants, and false negative results stemming from stringent variant interpretation. False positive results may result from inaccuracies in public databases. Additional studies in consanguineous populations will determine whether exome-based carrier screening should be recommended to all couples undergoing PGD.

血缘关系在全球许多地区都很常见，它与常染色体隐性遗传 (AR) 遗传疾病的风险增加有关。因此，因一种孟德尔疾病接受植入前遗传学诊断 (PGD) 的近亲夫妇可能会增加患有第二种不相关的 AR 遗传疾病的儿童的风险。我们检查了外显子组分析在血缘与非血缘人群中对其他 AR 疾病的携带者筛查的产量，超出了初步诊断。在无视主要分子诊断后，评估了来自 102 个近亲家庭和 105 个非近亲对照的三个外显子组的父母样本的共享携带者状态。结果根据疾病严重程度进行了细分。²  = 8.0565，p值 < 0.005）。根据个体外显子组计算的较高近交系数值与中度至重度严重疾病的次要共享携带者状态相关（r  = 0.17，p值 < 0.0125)。我们的研究结果表明，接受 PGD 的近亲夫妇患第二种中度至极重度遗传病的风险增加。由于无法检测到深内含子变异、未评估拷贝数变异以及源自严格变异解释的假阴性结果，该研究低估了二次共享携带者状态的发生率。公共数据库中的不准确可能会导致假阳性结果。对近亲人群的进一步研究将确定是否应向所有接受 PGD 的夫妇推荐基于外显子组的携带者筛查。