TY - JOUR
T1 - Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea-acanthocytosis
AU - Tomiyasu, Akiyuki
AU - Nakamura, Masayuki
AU - Ichiba, Mio
AU - Ueno, Shuichi
AU - Saiki, Shinji
AU - Morimoto, Mizuki
AU - Kobal, Jan
AU - Kageyama, Yasufumi
AU - Inui, Toshio
AU - Wakabayashi, Koichi
AU - Yamada, Tatsuo
AU - Kanemori, Yuji
AU - Jung, Hans H.
AU - Tanaka, Haruhiko
AU - Orimo, Satoshi
AU - Afawi, Zaid
AU - Blatt, Ilan
AU - Aasly, Jan
AU - Ujike, Hiroshi
AU - Babovic-Vuksanovic, Dusica
AU - Josephs, Keith A.
AU - Tohge, Rie
AU - Rodrigues, Guilherme Riccioppo
AU - Dupré, Nicolas
AU - Yamada, Hidetaka
AU - Yokochi, Fusako
AU - Kotschet, Katya
AU - Takei, Takanobu
AU - Rudzińska, Monika
AU - Szczudlik, Andrzej
AU - Penco, Silvana
AU - Fujiwara, Masaki
AU - Tojo, Kana
AU - Sano, Akira
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Chorea-acanthocytosis
KW - Chorein
KW - Copy number variations
KW - VPS13A
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U2 - 10.1002/ajmg.b.31206
DO - 10.1002/ajmg.b.31206
M3 - Article
C2 - 21598378
AN - SCOPUS:79958719790
SN - 1552-4841
VL - 156
SP - 620
EP - 631
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -