A unique case of neurodevelopmental disorders and epilepsy linked to WDR45 variant inheritance and maternal mosaicism

Abstract

This paper reports a case of a WDR45 variant inherited from an asymptomatic low-percentage mosaic mother. The proband boy was found to have significant psychomotor developmental delay, epilepsy, and abnormal liver function at four months of age, and a hemizygous variant WDR45 c.867_869dupGTA (p.Y290*) was detected by high throughput sequencing, which has an ACMG rating of likely pathogenic variant. The same variant was detected by high-throughput sequencing of the amniotic fluid of the fetus at his mother's next pregnancy. Eventually, the same variant was detected in mosaic status in the unaffected mother by target capture-based deep sequencing of the asymptomatic mother, with a mutation load of 4.06 %.

Keywords: Clinical exome sequencing; Mosaicism; Neurodevelopmental disorders; Sanger sequencing; Target capture-based deep sequencing; WDR45.