Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The development of whole‐exome sequencing (WES) and whole‐genome sequencing (WGS) for clinical purposes now allows the identification of multiple pathogenic variants in patients with a rare disease. This occurs even when a single causative gene was initially suspected. We report the case of an 8‐year‐old patient with global developmental delays and dysmorphic features, with a possibly pathogenic variant in three distinct genes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Trio‐based exome sequencing was performed by IntegraGen SA (Evry, France), on an Illumina HiSeq4000 (Illumina, San Diego, CA, USA). Sanger sequencing was performed to confirm the variants that were found.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>WES showed the presence of three possibly deleterious variants: <jats:italic>KMT2A</jats:italic>: c.9068delA;p.Gln3023Argfs*3 <jats:italic>de novo</jats:italic>, <jats:italic>PAX3</jats:italic>: c.530C>G;p.Ala177Gly <jats:italic>de novo</jats:italic> and <jats:italic>DLG3</jats:italic>: c.127delG;p.Asp43Metfs*22 hemizygous inherited from the mother. <jats:italic>KMT2A</jats:italic> pathogenic variants are involved in Wiedemann‐Steiner syndrome, and <jats:italic>PAX3</jats:italic> is the gene responsible for Waardenburg syndrome. <jats:italic>DLG3</jats:italic> variants have been described in a non‐syndromic X‐related intellectual disability.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Considering the dysmorphic features and intellectual disability presented by this patient, these three variants were imputed as pathogenic and their association was considered responsible for his phenotype. Dual molecular diagnoses have already been found by WES in several cohorts with an average of diagnostic yield of 7%. This case demonstrates and reminds us of the importance of analyzing exomes rigorously and exhaustively because, in some cases (< 10%), it can explain superimposed traits or blended phenotypes.</jats:p></jats:sec>