New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families
New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families
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DOI：
10.1016/s0378-1119(02)00416-x
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发表时间：
2002-02-20
期刊：
影响因子：
3.5
通讯作者：
Szepetowski, P
中科院分区：
文献类型：
--
作者：
Roll, P;Massacrier, A;Szepetowski, P
共转运蛋白是一类主要的蛋白质，它们利用离子梯度驱动底物主动转运进入细胞。在人类染色体16p12-p11上发现了一个编码钠/葡萄糖共转运蛋白家族成员的新基因KST1。该基因组区域包含一个主要基因，负责婴儿惊厥和阵发性运动障碍综合征（ICCA综合征），作为常染色体显性性状遗传，以及良性家族性婴儿惊厥（BFIC）。采用兔同源DNA （cDNA）与相应的人类基因组序列的硅比对、人脑RNA逆转录聚合酶链反应、cDNA末端的5′和3′快速扩增等方法，确定了人类KST1基因的整个编码序列。该基因被分成16个外显子，预测的蛋白含有675个氨基酸，包含14个跨膜结构域。它与钠-葡萄糖转运蛋白I共转运蛋白具有显著的同源性。由外显子6的跳跃引起的选择性剪接转录物导致预测的蛋白质缺乏第4跨膜结构域。由于离子转运体是包括阵发性疾病在内的多种人类疾病的良好候选者，因此在四个具有ICCA或BFIC综合征的家族中进行了突变搜索。未发现致病性突变，但发现了几个具有氨基酸交换的多态性变异。由于其在人体组织中的广泛表达，人类KST1基因可能与人类染色体16p12-p11上的其他几种疾病有关(C) 2002 Elsevier Science B.V.版权所有。
Cotransporters represent a major class of proteins that make use of ion gradients to drive active transport of substrate into cells. A new human gene, KST1, encoding a member of the sodium/glucose cotransporter family, was identified onto human chromosome 16p12-p11. This genomic region contains a major gene responsible for a syndrome of infantile convulsions and paroxysmal dyskinesia (ICCA syndrome), inherited as an autosomal dominant trait, as well as for benign familial infantile convulsions (BFIC). The entire coding sequence of the human KST1 gene was determined using a combination of methods including in silico comparison of its rabbit orthologous DNA complementary to RNA (cDNA) to the corresponding human genomic sequences, reverse transcription-polymerase chain reaction on human brain RNA, 5' and 3' rapid amplification of cDNA ends. The gene is divided into 16 exons and the predicted protein of 675 amino acids contains 14 trans membrane domains. It shares significant homology to the sodium-glucose transporter I cotransporter proteins. An alternatively spliced transcript resulting from the skipping of exon 6 led to a predicted protein lacking the 4th transmembrane domain. As ion transporters are good candidates for a large variety of human diseases, including paroxysmal disorders, a mutation search was performed in four families with ICCA or BFIC syndromes. No pathogenic mutation was found, although several polymorphic variants with amino acids exchanges were identified. Due to its broad expression in human tissues, the human KST1 gene could be involved in several other diseases mapped to human chromosome 16p12-p11 (C) 2002 Elsevier Science B.V. All rights reserved.