Premium
Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea‐acanthocytosis
Author(s) -
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,
BabovicVuksanovic Dusica,
Josephs Keith A.,
Tohge Rie,
Rodrigues Guilherme Riccioppo,
Dupré Nicolas,
Yamada Hidetaka,
Yokochi Fusako,
Kotschet Katya,
Takei Takanobu,
Rudzińska Monika,
Szczudlik Andrzej,
Penco Silvana,
Fujiwara Masaki,
Tojo Kana,
Sano Akira
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31206
Subject(s) - chorea , genetics , gene , exon , copy number variation , mutation , biology , compound heterozygosity , medicine , pathology , genome , disease
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. © 2011 Wiley‐Liss, Inc.