High-throughput STELA provides a rapid test for the diagnosis of telomere biology disorders.
High-throughput STELA provides a rapid test for the diagnosis of telomere biology disorders.
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高通量STELA为端粒生物学疾病的诊断提供了一种快速检测方法。
DOI：
10.1007/s00439-021-02257-4
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发表时间：
2021-06
期刊：
影响因子：
5.3
通讯作者：
Baird DM
中科院分区：
文献类型：
--
作者：
Norris K;Walne AJ;Ponsford MJ;Cleal K;Grimstead JW;Ellison A;Alnajar J;Dokal I;Vulliamy T;Baird DM
端粒生物学疾病是由于端粒维持所需的基因突变而引起的复杂临床病症。端粒长度已被用作这些疾病患者诊断检查的一部分；在这里，我们测试了高通量 STELA (HT-STELA) 为此目的的实用性。 HT-STELA 适用于未受影响个体队列 (n = 171) 和突变携带者回顾性队列 (n = 172)。 HT-STELA 显示出较低的测量误差，批间和批内方差系数分别为 2.3% 和 1.8%。虽然未受影响个体的端粒长度随着年龄的增长而下降，但突变携带者的端粒长度似乎有所增加，因为在年轻个体（< 20 岁）中检测到较短的端粒占优势。这些个体受到的影响更严重，年龄调整的端粒长度差异可用于对队列的总体生存进行分层（风险比 = 5.6（1.5–20.5）；p < 0.0001）。无症状突变携带者的端粒长度短于对照组（p<0.0001），但比有症状突变携带者长（p<0.0001），端粒长度异质性取决于诊断和突变状态。我们的数据表明，HT-STELA 能够检测其他方法不易检测到的短端粒长度，这意味着它可以提供强大的诊断辨别和预后信息。快速格式和低测量误差表明 HT-STELA 是一种新的高质量实验室测试，用于潜在端粒病的临床诊断。在线版本包含可在 10.1007/s00439-021-02257-4 获取的补充材料。
Telomere biology disorders are complex clinical conditions that arise due to mutations in genes required for telomere maintenance. Telomere length has been utilised as part of the diagnostic work-up of patients with these diseases; here, we have tested the utility of high-throughput STELA (HT-STELA) for this purpose. HT-STELA was applied to a cohort of unaffected individuals (n = 171) and a retrospective cohort of mutation carriers (n = 172). HT-STELA displayed a low measurement error with inter- and intra-assay coefficient of variance of 2.3% and 1.8%, respectively. Whilst telomere length in unaffected individuals declined as a function of age, telomere length in mutation carriers appeared to increase due to a preponderance of shorter telomeres detected in younger individuals (< 20 years of age). These individuals were more severely affected, and age-adjusted telomere length differentials could be used to stratify the cohort for overall survival (Hazard Ratio = 5.6 (1.5–20.5); p < 0.0001). Telomere lengths of asymptomatic mutation carriers were shorter than controls (p < 0.0001), but longer than symptomatic mutation carriers (p < 0.0001) and telomere length heterogeneity was dependent on the diagnosis and mutational status. Our data show that the ability of HT-STELA to detect short telomere lengths, that are not readily detected with other methods, means it can provide powerful diagnostic discrimination and prognostic information. The rapid format, with a low measurement error, demonstrates that HT-STELA is a new high-quality laboratory test for the clinical diagnosis of an underlying telomeropathy. The online version contains supplementary material available at 10.1007/s00439-021-02257-4.
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DOI：
10.1016/j.mrfmmm.2011.04.003
发表时间：
2012-02-01
影响因子：
2.3
作者：
Aubert, Geraldine;Hills, Mark;Lansdorp, Peter M.
通讯作者：
Lansdorp, Peter M.
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.6
作者：
LEVY, MZ;ALLSOPP, RC;HARLEY, CB
通讯作者：
HARLEY, CB
影响因子：
5.6
作者：
Khincha PP;Dagnall CL;Hicks B;Jones K;Aviv A;Kimura M;Katki H;Aubert G;Giri N;Alter BP;Savage SA;Gadalla SM
通讯作者：
Gadalla SM
影响因子：
30.8
作者：
Baird, DM;Rowson, J;Kipling, D
通讯作者：
Kipling, D