FMR1 等位基因大小分布在 35000 名男性和女性中：发育迟缓与普通人群队列的比较。
FMR1 allele size distribution in 35,000 males and females: a comparison of developmental delay and general population cohorts.
机构信息
Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
出版信息
Genet Med. 2018 Dec;20(12):1627-1634. doi: 10.1038/gim.2018.52. Epub 2018 Mar 29.
PURPOSE
Developmental delay phenotypes have been associated with FMR1 premutation (PM: 55-200 CGG repeats) and "gray zone" (GZ: 45-54 CGG repeats) alleles. However, these associations have not been confirmed by larger studies to be useful in pediatric diagnostic or screening settings.
METHODS
This study determined the prevalence of PM and GZ alleles in two independent cohorts of 19,076 pediatric referrals to developmental delay diagnostic testing through Victorian Clinical Genetics Service (cohort 1: N = 10,235; cohort 2: N = 8841), compared with two independent general population cohorts (newborn screening N = 1997; carrier screening by the Victorian Clinical Genetics Service prepair program N = 14,249).
RESULTS
PM and GZ prevalence rates were not significantly increased (p > 0.05) in either developmental delay cohort (male PM: 0.12-0.22%; female PM: 0.26-0.33%; male GZ: 0.68-0.69%; female GZ: 1.59-2.13-%) compared with general population cohorts (male PM: 0.20%; female PM: 0.27-0.82%; male GZ: 0.79%; female GZ: 1.43-2.51%). Furthermore, CGG size distributions were comparable across datasets, with each having a modal value of 29 or 30 and ~1/3 females and ~1/5 males having at least one allele with ≤26 CGG repeats.
CONCLUSION
These data do not support the causative link between PM and GZ expansions and developmental-delay phenotypes in pediatric settings.
目的
发育迟缓表型与脆性 X 智力低下 1 号基因（FMR1）前突变（PM：55-200CGG 重复）和“灰色地带”（GZ：45-54CGG 重复）等位基因有关。然而，这些关联尚未通过更大的研究得到证实，在儿科诊断或筛查环境中没有实际用途。
方法
本研究通过维多利亚临床遗传学服务（队列 1：N=10235；队列 2：N=8841），对 19076 例儿科发育迟缓诊断检测的独立队列中的 PM 和 GZ 等位基因的发生率进行了测定，并与两个独立的一般人群队列（新生儿筛查 N=1997；维多利亚临床遗传学服务的携带者筛查 prepair 项目 N=14249）进行了比较。
结果
在两个发育迟缓队列中，PM 和 GZ 的患病率均无明显升高（p＞0.05）（男性 PM：0.12-0.22%；女性 PM：0.26-0.33%；男性 GZ：0.68-0.69%；女性 GZ：1.59-2.13%），与一般人群队列相比（男性 PM：0.20%；女性 PM：0.27-0.82%；男性 GZ：0.79%；女性 GZ：1.43-2.51%）。此外，CGG 大小分布在各数据集之间具有可比性，每个数据集的模态值均为 29 或 30，约 1/3 的女性和约 1/5 的男性至少有一个等位基因的 CGG 重复数≤26。
结论
这些数据不支持 PM 和 GZ 扩展与儿科发育迟缓表型之间的因果关系。
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