Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Neurosci Res. 2011 Mar;69(3):196-202. doi: 10.1016/j.neures.2010.12.001. Epub 2010 Dec 9.
Neuroacanthocytosis syndromes are mainly comprised of two diseases: chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). There is a high incidence of psychiatric disorders such as mood disorder and schizophrenia among neuroacanthocytosis patients. We hypothesized that neuroacanthocytosis-related-genes might be associated with susceptibility to these psychiatric disorders. We performed a comprehensive mutation screen of VPS13A and XK, the gene responsible for ChAc and MLS, respectively, in 85 mood disorder subjects and XK in 86 schizophrenia subjects and compared the variants to 100 or more control alleles. We also performed copy number variation (CNV) analysis in 72 mood disorder subjects and 86 schizophrenia subjects. We identified three non-synonymous, two synonymous and six intron variants in mood disorder subjects and a novel GAT triplet repeat polymorphism in VPS13A. By CNV analysis, we identified a heterozygous exon 60-61 deletion in VPS13A in one mood disorder subject. We identified one non-synonymous and one intron variant in mood disorder and schizophrenia subjects, respectively, in XK. The presence of a pathogenic mutation or a potentially functional variant in mood disorder or schizophrenia subjects suggests that neuroacanthocytosis-related-genes might be involved in the pathogenesis of these psychiatric disorders.
舞蹈棘红细胞增多症（ChAc）和 McLeod 综合征（MLS）。神经棘红细胞增多症患者中精神障碍（如心境障碍和精神分裂症）的发病率较高。我们假设神经棘红细胞增多症相关基因可能与这些精神障碍的易感性有关。我们对 85 名心境障碍患者的 VPS13A 和 XK（分别负责 ChAc 和 MLS 的基因）以及 86 名精神分裂症患者的 XK 进行了全面的突变筛查，并将这些变体与 100 个或更多的对照等位基因进行了比较。我们还对 72 名心境障碍患者和 86 名精神分裂症患者进行了拷贝数变异（CNV）分析。我们在心境障碍患者中发现了三个非同义、两个同义和六个内含子变体，以及 VPS13A 中的一个新 GAT 三核苷酸重复多态性。通过 CNV 分析，我们在一名心境障碍患者中发现了 VPS13A 的杂合子外显子 60-61 缺失。我们在心境障碍和精神分裂症患者中分别发现了一个非同义突变和一个内含子变体。在心境障碍或精神分裂症患者中存在致病性突变或潜在功能变体表明，神经棘红细胞增多症相关基因可能参与这些精神障碍的发病机制。
