Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.

智力障碍（ID）占总人口的 1%，它是由遗传和/或环境因素之间的相互作用引起的。导致 ID 发展的遗传成分具有高度异质性，即使患者具有相同的病理变异和/或属于同一家族，疾病的表型和严重程度也会有所不同。在此，我们报道了一个伊朗家庭中的两个有身份证的男性兄弟姐妹。通过全外显子组测序方法，受中等ID影响的哥哥在KCNQ3基因中表现出从头错义变异，而另一个患有严重疾病的兄弟表现出新的框内缺失。在UBE3A基因。先前已将这两种变体归因于相似的临床表型。此外，KCNQ3基因的一个遗传变异传给了他的儿子，他的儿子患有轻度 ID。据我们所知，所有与KCNQ3相关的发育迟缓的个体都表现出KCNQ3基因的从头变异。因此，这个家族性病例表现出较温和的表型，可能会扩展KCNQ3致病变异的临床谱。此外，本报告强调了基因分析的临床评估和无偏见评估的重要性。