A novel VPS13A mutation in an Iranian family with Chorea-Acanthocytosis

Area of Science:

• Genetics
• Neuroscience
• Rare Diseases

Background:

• Chorea-Acanthocytosis (ChAc) is a rare, inherited neurodegenerative disorder.
• It is characterized by progressive neurological decline and distinctive red blood cell morphology (acanthocytosis).
• Biallelic mutations in the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene are the established cause of ChAc.

Purpose of the Study:

• To report a novel VPS13A gene mutation associated with Chorea-Acanthocytosis.
• To describe the clinical and genetic findings in two affected Iranian siblings.
• To contribute to understanding the genetic diversity of ChAc in the Iranian population.

Main Methods:

• Clinical evaluation of two brothers presenting with ChAc symptoms.
• Whole exome sequencing (WES) for genetic analysis.
• Segregation analysis in the parents to confirm inheritance pattern.

Main Results:

• Identification of a novel homozygous frameshift mutation (c.6348delA, p.K2117Nfs*16) in exon 47 of the VPS13A gene in both affected brothers.
• Parents were confirmed as heterozygous carriers for the identified mutation.
• The mutation was absent in unaffected individuals, confirming its pathogenicity.

Conclusions:

• This study reports a previously undescribed homozygous frameshift mutation in VPS13A causing Chorea-Acanthocytosis.
• This finding expands the spectrum of VPS13A mutations linked to ChAc, particularly within the Iranian population.
• Highlights the importance of genetic testing for diagnosing neuroacanthocytosis syndromes.