A de novo frame-shift mutation in the tuberin gene.
A de novo frame-shift mutation in the tuberin gene.
复制标题
马铃薯蛋白基因的从头移码突变。
DOI：
10.1093/hmg/4.8.1471
复制
发表时间：
1995
影响因子：
3.5
通讯作者：
Gilbert,JR
中科院分区：
文献类型：
--
作者：
Kumar,A;Wolpert,C;Kandt,RS;Segal,J;Pufky,J;Roses,AD;Pericak-Vance,MA;Gilbert,JR
多发性硬化症（TSC）是一种常染色体显性遗传的细胞迁移、增殖和分化障碍，影响脑、肾、心、肺和皮肤等多种器官系统。TSC表现出不完全表达和可变表达，并且即使在同一家族的成员中，表型也可以相当多样。表型表达从精神发育迟滞、癫痫发作和特征性皮肤病变变化到仅良性皮肤病变的较温和表型。TSC的估计发病率为1：6000至1：10000（活产）。约50%的TSC病例为散发病例（即无TSC家族史）。这些散发病例通常被认为是新的突变。然而，TSC的可变表达和非特异性表达常常使携带者状态的确定不确定。通过直接突变分析明确识别TSC基因携带者的能力将对这种疾病的遗传咨询产生重大影响。遗传连锁研究表明，两个TSC基因座位于染色体9q34（TSC 1）和16p13。3（TSC 2）。这两种类型在分离的TSC家族中以相等的频率发生。TSC2基因座的（块茎素）基因于1993年分离（1）。TSC1基因尚未被发现。TSC2基因识别一个5474 bp长的转录本，包含40个已知的外显子（Dr M. Nellist，个人通信）。迄今为止，仅在患者中报告了大小为0.5至大于10 kb的基因内缺失突变，已知突变占TSC病例的不到5%（1，2）。在TSC患者中尚未报告确定的TSC 2单碱基对突变。
Tuberous sclerosis complex (TSC), one of the phakomatoses, is an autosomal dominant disorder of cell migration, proliferation and differentiation that affects numerous organ systems such as brain, kidneys, heart, lungs and skin. TSC exhibits both incomplete penetrance and variable expression and the phenotype can be quite diverse even among members of the same family. The phenotypic expression varies from mental retardation, seizures and characteristic skin lesions to a milder phenotype of only benign cutaneous lesions. TSC has an estimated incidence of 1: 6000 to 1: 10 000 (live births). Approximately 50% of the TSC cases present as sporadic cases (ie no family history of TSC). These sporadic cases are often thought to be new mutations. The variable expression and nonpenetrance that characterizes TSC, however, often renders carrier status determination inconclusive. The ability to definitively identify TSC gene carriers via direct mutational analysis would have a significant impact in genetic counseling in this disorder.• Genetic linkage studies demonstrated two TSC loci located at chromosomes 9q34 (TSC1) and 16pl3. 3 (TSC2). These two types occur with equal frequency in segregating TSC families. The (tuberin) gene for the TSC2 locus was isolated in 1993 (1). The TSC1 gene has not yet been identified. The TSC2 gene recognizes a 5474 bp long transcript and contains 40 known exons (Dr M. Nellist, personal communication). To date, only intragenic deletional mutations, ranging in size from 0.5 to greater than 10 kb, have been reported in patients and known mutations account for less than 5% of TSC cases (1, 2). No defined TSC2 single base pair mutations have yet been reported in TSC patients.