Novel loss-of-function mutations in VPS13A cause chorea-acanthocytosis in two families.

INTRODUCTION

Chorea-acanthocytosis (ChAc) is the most common subtype of neuroacanthocytosis (NA) caused by mutations in VPS13A (vacuole protein sorting-associated protein 13A). ChAc is characterized by the presence of spherocytes and neurological symptoms. This article reports two families with ChAc and summarizes some suggestive characteristics, providing an effective basis for clinicians to screen ChAc in the early stage and effectively reduce the misdiagnosis and missed diagnosis of this disease.

METHODS

We first performed whole-exome sequencing (WES) and confirmed three NA cases in two families. Detailed clinical and peripheral blood smear analyses are presented, supplemented by molecular electron microscopy to assess erythrocyte ultrastructure. To further evaluate the functional impact of candidate variants, we additionally performed RNA splicing analysis.

RESULTS

Three ChAc cases in two families were identified. Clinically, almost all cases presented initial movement disorders, and Elevated creatine kinase (CK) level. Besides, both peripheral blood smear and scanning electron microscopy revealed characteristic acanthocytes.

CONCLUSIONS

This study provides key clinical indicators for early ChAc screening: early movement disorders combined with persistently elevated CK levels and significant acanthocytosis on peripheral blood smear. We further identified three novel VPS13A mutations, expanding the variant spectrum and confirming clinical heterogeneity in ChAc.