A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.

先前与显性遗传相关的几个基因中已经描述了具有共显性或隐性遗传的家族子集。这些隐性家族与显性家族表现出相似、更严重甚至完全不同的表型。我们报告了第一批在三个与显性遗传相关的基因中携带纯合疾病相关变异的患者：CACNA1A基因中的功能丧失变异和RET和SLC20A2中的两个错义变异基因，分别。所有患者都表现出比相应的典型优势形式更严重的临床表型。我们建议这三个基因的共同显性或隐性遗传可以解释与其同源显性表型中记录的表型差异。我们的结果强化了遗传学家在进行 WES 变异解释时应该意识到基因中可能存在的不同遗传形式。我们还证明有必要改进与基因相关的表型和遗传模式，以避免 WES 分析过程中的失败，从而提高 WES 诊断能力，从而使患者受益。