The identification of two pathogenic variants in a family with mild and severe forms of developmental delay

Abstract

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 theKCNQ3gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in theUBE3Agene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in theKCNQ3gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals withKCNQ3-related developmental delay show de novo variants in theKCNQ3gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum ofKCNQ3pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.