Unequal crossover recombination -: population screening for PHOX2B gene polyalanine polymorphism using CE
Unequal crossover recombination -: population screening for PHOX2B gene polyalanine polymorphism using CE
复制标题
DOI：
10.1002/elps.200600383
复制
发表时间：
2007-03-01
期刊：
影响因子：
2.9
通讯作者：
Hsu, Su-Ming
中科院分区：
文献类型：
--
作者：
Hung, Chia-Cheng;Su, Yi-Ning;Hsu, Su-Ming
先天性中枢性低通气综合征（CCHS）是一种罕见的神经系统疾病，其特征是睡眠时自主神经系统对呼吸的控制异常。配对样同源框2B（PHOX 2B）基因的突变，包括点突变、移码和多聚丙氨酸扩增，与CCHS的发病机制相关。在这项研究中，PHOX 2B突变分析7 CCHS患者，他们的家庭成员，和1520名健康人从一般人群中使用CE提供高灵敏度和分辨率的PHOX 2B多聚丙氨酸多态性筛查。PHOX 2B基因中的7个突变，包括2个移码突变和5个多聚丙氨酸扩展的20个残基的多聚丙氨酸道，被确定。在携带PHOX 2B突变的CCHS患者中观察到的各种表型表明扩展等位基因的大小与CCHS风险相关。此外，在健康人群中，等位基因和基因型分布也存在显著差异。等位基因（GCN）（20）和（GCN）（15）的群体发病率最高，分别为94.84%和4.51%，其余等位基因（GCN）（13）和（GCN）（7）的群体发病率分别为0.59%和0.06%。因此，已经证明CE可用于改善PHOX 2B基因中聚丙氨酸扩增的检测。有吸引力的替代方法是一个很有前途的工具，用于检测涉及三核苷酸重复序列的疾病。
Congenital central hypoventilation syndrome (CCHS) is a rare neurological disorder characterized by abnormal autonomic central nervous system control of breathing during sleep. Mutations in the paired-like homeobox 2B (PHOX2B) gene, including point mutation, frameshift, and polyalanine expansion, are associated with the pathogenesis of CCHS. In this study, PHOX2B mutations were analyzed in seven CCHS patients, their family members, and 1520 healthy individuals from the general population using CE to provide high sensitivity and resolution screening for the PHOX2B polyalanine polymorphism. Seven mutations in the PHOX2B gene, including two frameshift mutations and five polyalanine expansions in the 20-residue polyalanine tract, were identified. The various phenotypes observed in CCHS patients with PHOX2B mutations suggest that the size of the expansion allele is associated with the CCHS risk. In addition, significant differences were found in allele and genotype distributions between the healthy individuals. Alleles (GCN)(20) and (GCN)(15) had the highest population incidence rates of 94.84 and 4.51%, respectively, with the remaining alleles, (GCN)(13) and (GCN)(7), accounting for 0.59 and 0.06%, respectively. Therefore, it has been demonstrated that CE can be used to improve the detection of polyalanine expansions in the PHOX2B gene. The attractive alternative method is a promising tool for the detection of disorders involving trinucleotide repeat tracts.