Challenges in Establishing the Diagnosis of PRRT2-Related Dystonia: Recurrent Pathogenic Variants in a Homopolymeric Stretch

Abstract

Re-analysis of next-generation sequencing (NGS) data can help to resolve undiagnosed cases. We report on two patients with dystonia to illustrate how stringent NGS-variant filtering criteria can lead to missed diagnoses in the context of variants lying in a homopolymeric nucleotide tract; at the same time, relaxing bioinformatic-filter settings can yield false-positive pathogenic variant-hits in the same homopolymeric stretch, further complicating the NGS-based diagnostic process.

Keywords

• PRRT2-Related Dystonia
• Recurrent Pathogenic Variants
• Homopolymeric Stretch