Novel VPS13A Gene Mutations in a South Asian, Indian Patient with Chorea‑acanthocytosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.279653
Source of Support: None, Conflict of Interest: None
Chorea-acanthocytosis (ChAc), a subtype of neuroacanthocytosis, is autosomal recessive disorder. It shows a variety of hyperkinetic and hypokinetic movement disorders with elevated levels of acanthocytosis and progressive degeneration of basal ganglia. It has mutations in the VPS13A gene on chromosome 9q21. We report newly established double deletions on the VPS13A gene linked with typical ChAc, bilateral hippocampal sclerosis, and cognitive dysfunction.
A 42-year-old, right-handed, South Asian female from India visited our clinic for the treatment of epilepsy and orofacial involuntary movement. She was diagnosed with epilepsy when she had a generalized seizure at the age of 28. She also suffered cognitive decline. On examination, she had dysarthria and orolingual and phonic tics. There were no signs of Parkinsonism More Details, lip biting, dystonia, generalized chorea, amyotrophy, or areflexia. Montreal cognitive assessment revealed a score of 15/30 and cognitive decline of executive function, short term memory, and configuration. Laboratory findings showed hemoglobin of 9.7 g/dl, indicating anemia, and acanthocytes. Expression of Kell antigens on red blood cells was strong, and apolipoprotein B was normal. She also had elevated creatine phosphokinase, 1559 IU/l. T2-weighted MRI showed bilateral striatal atrophy [Figure 1]a, and bilateral hippocampal sclerosis. Electroencephalography showed epileptic discharges in the left anterotemporal cortex. Nerve conduction studies and electromyography were normal. We extracted RNA from whole blood sample cDNA for analysis and found a 7 bp deletion in exon1 of the VPS13A gene and a 4 bp deletion in exon 55. Both mutations are linked to frameshift, downstream codon stoppage [Figure 1]b. Using western blot analysis of chorein protein erythrocyte membrane fractionation, we established a corresponding band of full-length chorein for the patient and confirmed defects [Figure 1]c. These results provided molecular support for a diagnosis of a new type of ChAc. Convulsions disappeared after oral antiepileptic drugs were added to carbamazepine 450 mg/day, levetiracetam 2000 mg/day, and clonazepam 1.0 mg/day.
Comprehensive mutation screening for all 73 exons was performed and showed marked genotype-phenotype heterogeneity. However, double newly established compound heterozygous mutations are rare. This case may shed new light on compound heterozygous mutation on VPS13A gene and ChAc genesis.
The authors wish to thank Hanae Hiwatashi, MD, Department of Psychiatry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan, for her assistance in VPS13A gene assay. We also wish to thank Masako Watanabe, MD, Shinjuku Neuro Clinic, Tokyo, Japan, for the exam and analysis of electroencephalogram, Akira Midorikawa, Prof., Department of Psychology, Faculty of Letters, Chou University, Tokyo, Japan, for support of psychological assessment, and Michael W. Miller, Prof., Postgraduate School of Medicine, University of Tokyo, Tokyo, Japan, for help with the manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of Kagoshima University School of Medical and Dental Sciences approved this study, and it was performed according to the Declaration of Helsinki.
Informed consent was obtained from the individual participants included in the study.
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