Landowska Aleksandra, Rzońca Sylwia, Bal Jerzy, Gos Monika
Zakład Genetyki Medycznej, Instytut Matki i Dziecka, Warszawa, Polska.
Dev Period Med. 2018;22(1):14-21. doi: 10.34763/devperiodmed.20182201.1421.
Fragile X syndrome (FXS) is the second most common inherited cause of intellectual disability (ID), after Down syndrome. The severity of ID in FXS patients varies and depends mainly on the patient's sex. Besides intellectual disorders, additional symptoms, such as psychomotor delay, a specific behavioral phenotype, or emotional problems are present in FXS patients. In over 99% of the cases, the disease is caused by the presence of a dynamic mutation in the FMR1 gene localized on the X chromosome. Due to the expansion of CGG nucleotides (over 200 repeats), FMR1 gene expression is decreased and results in the significant reduction of the FMRP protein level. The CGG expansion to premutation range (55-200 CGG repeats) is equivalent to the FXS carrier status and may cause FMR1-dependent disorders - fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). In contrast to FXS, clinical symptoms of these diseases occur later in adulthood. The aim of the article is to present the knowledge about the molecular background and epidemiology of fragile X syndrome and other FMR1-related disorders.
脆性X综合征（FXS）是仅次于唐氏综合征的第二大常见遗传性智力障碍（ID）病因。FXS患者ID的严重程度各不相同，主要取决于患者的性别。除智力障碍外，FXS患者还存在其他症状，如精神运动发育迟缓、特定的行为表型或情绪问题。在超过99%的病例中，该病是由位于X染色体上的FMR1基因存在动态突变引起的。由于CGG核苷酸的扩增（超过200次重复），FMR1基因表达降低，导致FMRP蛋白水平显著降低。CGG扩增到前突变范围（55 - 200次CGG重复）等同于FXS携带者状态，并可能导致FMR1相关疾病——脆性X相关原发性卵巢功能不全（FXPOI）和脆性X相关震颤/共济失调综合征（FXTAS）。与FXS不同，这些疾病的临床症状在成年期后期出现。本文的目的是介绍有关脆性X综合征及其他FMR1相关疾病的分子背景和流行病学的知识。
