Development of Genetic Testing for Fragile X Syndrome and Associated Disorders, and Estimates of the Prevalence of FMR1 Expansion Mutations.
Development of Genetic Testing for Fragile X Syndrome and Associated Disorders, and Estimates of the Prevalence of FMR1 Expansion Mutations.
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DOI：
10.3390/genes7120110
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发表时间：
2016-11-30
期刊：
影响因子：
3.5
通讯作者：
Murray A
中科院分区：
文献类型：
--
作者：
Macpherson JN;Murray A
1991年，三核苷酸（CGG）扩增被鉴定为脆性X综合征的主要突变机制，这预示着分子诊断遗传学的新篇章，并产生了对人类遗传性疾病突变机制的新观点，随着越来越多的常见遗传性神经发育障碍被归因于这类新的突变，这迅速成为一个中心范式（“动态突变”）。FMR 1基因中的CGG重复序列从“前突变”逐渐扩展到“全突变”，这为“谢尔曼悖论”提供了解释，就像其他基因中类似的扩展机制解释了其发病机制中的“预期”现象一样。后来，FMR 1前突变意外地被发现与另外两种不同的表型相关：原发性卵巢功能不全和震颤-共济失调综合征。这篇综述将提供一个历史的角度来看，程序的测试和报告脆性X综合征和相关疾病，和人口遗传学的FMR 1扩展，包括估计的患病率和影响AGG散置的速度和概率的扩展。
The identification of a trinucleotide (CGG) expansion as the chief mechanism of mutation in Fragile X syndrome in 1991 heralded a new chapter in molecular diagnostic genetics and generated a new perspective on mutational mechanisms in human genetic disease, which rapidly became a central paradigm (“dynamic mutation”) as more and more of the common hereditary neurodevelopmental disorders were ascribed to this novel class of mutation. The progressive expansion of a CGG repeat in the FMR1 gene from “premutation” to “full mutation” provided an explanation for the “Sherman paradox,” just as similar expansion mechanisms in other genes explained the phenomenon of “anticipation” in their pathogenesis. Later, FMR1 premutations were unexpectedly found associated with two other distinct phenotypes: primary ovarian insufficiency and tremor-ataxia syndrome. This review will provide a historical perspective on procedures for testing and reporting of Fragile X syndrome and associated disorders, and the population genetics of FMR1 expansions, including estimates of prevalence and the influence of AGG interspersions on the rate and probability of expansion.
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影响因子：
56.9
作者：
KREMER, EJ;PRITCHARD, M;RICHARDS, RI
通讯作者：
RICHARDS, RI
DOI：
10.1073/pnas.92.11.5199
发表时间：
1995-05-23
影响因子：
11.1
作者：
CHEN, XA;MARIAPPAN, SVS;GUPTA, G
通讯作者：
GUPTA, G
影响因子：
64.5
作者：
FU, YH;KUHL, DPA;CASKEY, CT
通讯作者：
CASKEY, CT
影响因子：
3
作者：
Berkenstadt, Michal;Ries-Levavi, Liat;Barkai, Gad
通讯作者：
Barkai, Gad
影响因子：
64.5
作者：
KUNST, CB;WARREN, ST
通讯作者：
WARREN, ST