Huntington's disease--like 2 can present as chorea-acanthocytosis

Area of Science:

• Neurogenetics
• Movement Disorders
• Molecular Genetics

Background:

• Autosomal dominant chorea-acanthocytosis is a rare neurodegenerative disorder.
• Huntington's disease-like 2 (HDL2) is a distinct condition characterized by progressive motor and cognitive decline.
• Acanthocytosis, the presence of abnormally shaped red blood cells, is a feature seen in some neurodegenerative disorders.

Purpose of the Study:

• To investigate the genetic basis of chorea-acanthocytosis in a family with a previously described autosomal dominant inheritance pattern.
• To determine if Huntington's disease-like 2 (HDL2) is associated with chorea-acanthocytosis.
• To evaluate the clinical and genetic overlap between HDL2 and chorea-acanthocytosis.

Main Methods:

• Genetic analysis was performed on three patients from a family with autosomal dominant chorea-acanthocytosis.
• CTG trinucleotide repeat expansion analysis of the junctophilin-3 gene was conducted.
• Peripheral blood smears were examined for acanthocytosis in patients with HDL2.

Main Results:

• Three patients diagnosed with autosomal dominant chorea-acanthocytosis were found to harbor the CTG trinucleotide repeat expansion mutation in the junctophilin-3 gene.
• This mutation is associated with Huntington's disease-like 2 (HDL2).
• Acanthocytosis was observed in one of six previously identified patients with HDL2, indicating a potential clinical overlap.

Conclusions:

• The junctophilin-3 gene CTG repeat expansion, linked to HDL2, can manifest as chorea-acanthocytosis.
• HDL2 should be considered in the differential diagnosis of chorea-acanthocytosis.
• Genetic testing for HDL2 may be warranted in patients presenting with chorea-acanthocytosis.