Fragile X premutation and associated health conditions: A review,Clinical Genetics

当前位置： X-MOL 学术 › Clin. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Fragile X premutation and associated health conditions: A review
Clinical Genetics ( IF 2.9 ) Pub Date : 2021-01-14 , DOI: 10.1111/cge.13924
Nattaporn Tassanakijpanich ₁ , Randi J Hagerman _{2,

3} , Juthamas Worachotekamjorn ₁

Affiliation

Fragile X syndrome (FXS) is the most common single gene disorder, which causes autism and intellectual disability. The fragile X mental retardation 1 (FMR1) gene is silenced when cytosine‐guanine‐guanine (CGG) triplet repeats exceed 200, which is the full mutation that causes FXS. Carriers of FXS have a CGG repeat between 55 and 200, which is defined as a premutation and transcription of the gene is overactive with high levels of the FMR1 mRNA. Most carriers of the premutation have normal levels of fragile X mental retardation protein (FMRP) and a normal intelligence, but in the upper range of the premutation (120–200) the FMRP level may be lower than normal. The clinical problems associated with the premutation are caused by the RNA toxicity associated with increased FMR1 mRNA levels, although for some mildly lowered FMRP can cause problems associated with FXS. The RNA toxicity causes various health problems in the carriers including but not limited to fragile X‐associated tremor/ataxia syndrome, fragile X‐associated primary ovarian insufficiency, and fragile X‐associated neuropsychiatric disorders. Since some individuals with neuropsychiatric problems do not meet the severity for a diagnosis of a “disorder” then the condition can be labeled as fragile X premutation associated condition (FXPAC). Physicians must be able to recognize these health problems in the carriers and provide appropriate management.

中文翻译：

脆性 X 前突变和相关健康状况：综述

脆性 X 综合征 (FXS) 是最常见的单基因疾病，可导致自闭症和智力障碍。当胞嘧啶-鸟嘌呤-鸟嘌呤 (CGG) 三联体重复超过 200 个时，脆性 X 智力迟钝 1 ( FMR1 ) 基因沉默，这是导致 FXS 的完整突变。FXS 携带者的 CGG 重复序列在 55 到 200 之间，这被定义为基因的前突变和转录过度活跃，FMR1 mRNA 水平高。大多数前突变携带者的脆性X智力迟钝蛋白（FMRP）水平正常，智力正常，但在前突变（120-200）的上限范围内，FMRP水平可能低于正常水平。与前突变相关的临床问题是由与增加相关的 RNA 毒性引起的。FMR1 mRNA 水平，尽管对于一些轻度降低的 FMRP 会导致与 FXS 相关的问题。RNA 毒性会导致携带者出现各种健康问题，包括但不限于脆性 X 相关的震颤/共济失调综合征、脆性 X 相关的原发性卵巢功能不全和脆性 X 相关的神经精神疾病。由于一些患有神经精神问题的人不符合诊断为“疾病”的严重程度，因此该病症可以标记为脆性 X 前突变相关病症 (FXPAC)。医生必须能够识别携带者的这些健康问题并提供适当的管理。

更新日期：2021-01-14

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11