Chorea-acanthocytosis: Homozygous 1-kb deletion in VPS13A detected by whole-genome sequencing

Neurol Genet. 2018 May 18;4(3):e242. doi: 10.1212/NXG.0000000000000242. eCollection 2018 Jun.

Abstract

Objective: To determine a molecular diagnosis for a large multigenerational family of South Asian ancestry with seizures, hyperactivity, and episodes of tongue biting.

Methods: Two affected individuals from the family were analyzed by whole-genome sequencing on the Illumina HiSeq X platform, and rare variants were prioritized for interpretation with respect to the phenotype.

Results: A previously undescribed, 1-kb homozygous deletion was identified in both individuals sequenced, which spanned 2 exons of the VPS13A gene, and was found to segregate in other family members.

Conclusions: VPS13A is associated with autosomal recessive chorea-acanthocytosis, a diagnosis consistent with the phenotype observed in this family. Whole-genome sequencing presents a comprehensive and agnostic approach for detecting diagnostic mutations in families with rare neurologic disorders.