Landowska Aleksandra, Rzońca Sylwia, Bal Jerzy, Gos Monika
Zakład Genetyki Medycznej, Instytut Matki i Dziecka, Warszawa, Polska.
Dev Period Med. 2018;22(1):22-32. doi: 10.34763/devperiodmed.20182201.2232.
The presence of dynamic mutation in the FMR1 gene localized on the X chromosome (Xq28) is the major cause of Fragile X syndrome. As this syndrome is quite frequently diagnosed in patients with intellectual disability and autism spectrum disorders, the genetic testing of the FMR1 gene is a routine procedure performed in these patients. Molecular methods based on the PCR technique are used commonly, as they allow to identify normal (up to 54 CGG repeats, including grey zone alleles - 45-54 CGG repeats), premutation (55-200 CGG repeats) and full mutation (>200 CGG repeats) alleles.The article presents the basic methods used in the molecular diagnosis of Fragile X syndrome and other FMR1-related disorders. The following methods are presented: a screening test with GeneScan analysis, TP-PCR based tests and methods used for methylation analysis. Their pros and cons, as well as the resulting interpretation are discussed. Moreover, there is a presentation of the molecular diagnostic scheme following European Molecular Genetics Quality Network guidelines used in the Department of Medical Genetics.
位于X染色体（Xq28）上的FMR1基因存在动态突变是脆性X综合征的主要病因。由于该综合征在智力残疾和自闭症谱系障碍患者中经常被诊断出来，因此对FMR1基因进行基因检测是这些患者的常规检查程序。基于PCR技术的分子方法被广泛使用，因为它们能够识别正常（多达54个CGG重复序列，包括灰色区域等位基因——45 - 54个CGG重复序列）、前突变（55 - 200个CGG重复序列）和全突变（>200个CGG重复序列）等位基因。本文介绍了用于脆性X综合征及其他FMR1相关疾病分子诊断的基本方法。介绍了以下方法：基因扫描分析筛查试验、基于TP-PCR的检测方法以及用于甲基化分析的方法。讨论了它们的优缺点以及结果解读。此外，还介绍了医学遗传学系按照欧洲分子遗传学质量网络指南进行的分子诊断方案。
