Case Report: Chorea-Acanthocytosis Presents as Epilepsy in a Consanguineous Family With a Nonsense Mutation of in VPS13A

Fang-Mei Luo,Ming-Xing Deng,Lv Liu,Liang-Liang Fan,Rong Yu

doi:10.3389/fnins.2021.604715

Abstract

Chorea-Acanthocytosis (ChAc), a rare autosomal recessive inherited neurological disorder, originated from variants in Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The main symptoms of ChAc contain hyperkinetic movements, seizures, cognitive impairment, neuropsychiatric symptoms, elevated serum biochemical indicators, and acanthocytes detection in peripheral blood smear. Recently, researchers found that epilepsy may be a presenting and prominent symptom of ChAc. Here, we enrolled a consanguineous family with epilepsy and non-coordinated movement. Whole exome sequencing was employed to explore the genetic lesion of the family. After data filtering, co-separation analysis was performed by Sanger sequencing and bioinformatics analysis, the homozygous nonsense variant (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A were identified which could be genetic factor of the patient. No other meaningful mutations were detected. This mutation (p.S2761X) led to a truncated protein in exon 60 of the VPS13A gene, was simultaneously absent in our 200 local control participants. The homozygous mutation (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A may be the first time be identified in ChAc patient with epilepsy. Our study assisted to the diagnosis of ChAc in this patient and contributed to the genetic diagnosis and counseling of families with ChAc presented as epilepsy. Moreover, we further indicated that epilepsy was a crucial phenotype in ChAc patients caused by VPS13A mutations.

Highlights

Chorea-acanthocytosis (ChAc, OMIM #200150) is a primary neurological disorder characterized by repetitive movements of various parts of the body and abnormal red blood cell shape (Velayos Baeza et al, 1993; Liu et al, 2018; Roulis et al, 2018)
Previous studies have revealed that autosomal-recessive mutations in the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene may be the genetic lesion of ChAc (Velayos Baeza et al, 1993)
An increasing number of studies have revealed that epilepsy may be a presenting and prominent symptom of ChAc caused by VPS13A mutations (Benninger et al, 2016; Weber et al, 2018)

Summary

INTRODUCTION

Chorea-acanthocytosis (ChAc, OMIM #200150) is a primary neurological disorder characterized by repetitive movements of various parts of the body and abnormal red blood cell shape (Velayos Baeza et al, 1993; Liu et al, 2018; Roulis et al, 2018). Previous studies have revealed that autosomal-recessive mutations in the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene may be the genetic lesion of ChAc (Velayos Baeza et al, 1993). Recent studies revealed that epilepsy may be a presenting and prominent symptom of ChAc caused by VPS13A mutations (Benninger et al, 2016; Weber et al, 2018). The peripheral blood samples of one patient (IV3) and three unaffected family members (IV-2, IV-4, and V1) were collected Clinical data, such as magnetic resonance imaging (MRI) and electroencephalogram (EEG), were recorded carefully. Further Sanger sequencing and bioinformatics analysis indicated that only the nonsense mutation (NM_033305.2: c.8282C>G, p.S2761X) in the VPS13A gene may be the genetic lesion of the patient (Figure 1E). According to ACMG guidelines (Richards et al, 2015), this mutation belongs to pathogenic (PVS1+PM2+PM3)

Discussion

CONCLUSIONS

ETHICS STATEMENT