A heterozygous germline deletion within USP8 causes severe neurodevelopmental delay with multiorgan abnormalities

In this study, we investigated an exome-negative patient with severe developmental delay, dysmorphic features, and multiorgan dysfunction by long-read sequencing, and identified a 22-kb de novo germline deletion withinUSP8 (chr15:50469966-50491995 [GRCh38]). The deletion involved the variant hotspot, one rhodanese domain, and two SH3 binding motifs, and was presumed to be generated through nonallelic homologous recombination throughAlu elements. Thus, the patient may have perturbation of the endosomal sorting system and mitochondrial autophagy through theUSP8 defect. This is the second reported case of a germline variant inUSP8.
Source: Journal of Human Genetics - Category: Genetics & Stem Cells Source Type: research