Novel Pathogenic Mutations and Copy Number Variations in the VPS13A Gene in Patients With Chorea-Acanthocytosis

作者：Tomiyasu Akiyuki; Nakamura Masayuki; Ichiba Mio; Ueno Shuichi; Saiki Shinji; Morimoto Mizuki; Kobal Jan; Kageyama Yasufumi; Inui Toshio; Wakabayashi Koichi; Yamada Tatsuo; Kanemori Yuji; Jung Hans H; Tanaka Haruhiko; Orimo Satoshi; Afawi Zaid; Blatt Ilan; Aasly Jan; Ujike Hiroshi; Babovic Vuksanovic Dusica; Josephs Keith A; Tohge Rie; Rodrigues Guilherme Riccioppo; Dupre Nicolas; Yamada Hidetaka; Yokochi Fusako; Kotschet Katya; Takei Takanobu; Rudzinska Monika

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2011, 156B(5): 620-631.

DOI：10.1002/ajmg.b.31206

• chorea-acanthocytosis
• VPS13A
• chorein
• copy number variations

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.

• 出版日期2011-7