A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22
A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22
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DOI：
10.1111/j.1540-8167.2007.00913.x
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发表时间：
2007-10-01
影响因子：
2.7
通讯作者：
Al-Gazali, Lihadh
中科院分区：
文献类型：
--
作者：
Bhuiyan, Zahurul A.;Hamdan, Mohamed A.;Al-Gazali, Lihadh
简介：此前，常染色体显性遗传性儿茶酚胺能多态性室性心动过速（CPVT [1]）被定位于染色体1 q42 -43，并在RYR 2中鉴定出致病突变。常染色体隐性CPVT（2）定位于染色体1 p13 -21，导致CASQ 2中突变的鉴定。在这项研究中，我们的目的是阐明一个新的变异的CPVT（3）在一个近交的阿拉伯家庭的临床表型，也描绘了染色体定位的基因引起CPVT（3）。方法和结果：在一个高度近交的家庭，CPVT的临床症状出现在儿童早期（7-12岁），并在四个案件中的三个，第一次出现的症状变成了致命的结果。受影响儿童的父母是一级堂兄弟，没有任何症状。分离分析提示为常染色体隐性遗传。使用多态性DNA标记的全基因组搜索将疾病位点映射到染色体7 p14-p22上的25 Mb间隔。在标记D 7S 493处获得的最大多点LOD评分为3.17。假定的候选基因，SP 4，神经肽Y，FKBP 9，FKBP 14，PDE 1C和TBX 20，在这个位点和周围的测序，没有发现任何突变。结论：我们已经确定了一种新的高度恶性常染色体隐性形式的CPVT和映射这种疾病的染色体7 p14-p22上的25 Mb的间隔。
Introduction: Previously, autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT [1]) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2. Autosomal recessive CPVT (2) was mapped to chromosome 1p13-21, leading to the identification of mutations in CASQ2. In this study, we aimed to elucidate clinical phenotypes of a new variant of CPVT (3) in an inbred Arab family and also delineate the chromosomal location of the gene causing CPVT (3).Methods and Results: In a highly inbred family, clinical symptoms of CPVT appeared early in childhood (7-12 years) and in three of the four cases, the first appearance of symptoms turned into a fatal outcome. Parents of the affected children were first-degree cousins and without any symptoms. Segregation analysis suggested an autosomal recessive inheritance. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 25-Mb interval on chromosome 7p14-p22. A maximal multipoint LOD score of 3.17 was obtained at marker D7S493. Sequencing of putative candidate genes, SP4, NPY, FKBP9, FKBP14, PDE1C, and TBX20, in and around this locus, did not reveal any mutation.Conclusions: We have identified a novel highly malignant autosomal recessive form of CPVT and mapped this disorder to a 25-Mb interval on chromosome 7p14-p22.