Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea-acanthocytosis

Akiyuki Tomiyasu, Masayuki Nakamura, Mio Ichiba, Shuichi Ueno, Shinji Saiki, Mizuki Morimoto, Jan Kobal, Yasufumi Kageyama, Toshio Inui, Koichi Wakabayashi, Tatsuo Yamada, Yuji Kanemori, Hans H. Jung, Haruhiko Tanaka, Satoshi Orimo, Zaid Afawi, Ilan Blatt, Jan Aasly, Hiroshi Ujike, Dusica Babovic-VuksanovicKeith A. Josephs, Rie Tohge, Guilherme Riccioppo Rodrigues, Nicolas Dupré, Hidetaka Yamada, Fusako Yokochi, Katya Kotschet, Takanobu Takei, Monika Rudzińska, Andrzej Szczudlik, Silvana Penco, Masaki Fujiwara, Kana Tojo, Akira Sano

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc.

Original languageEnglish (US)
Pages (from-to)620-631
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number5
StatePublished - Jul 2011


  • Chorea-acanthocytosis
  • Chorein
  • Copy number variations
  • VPS13A

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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