Todorov Tihomir, Todorova Albena, Kirov Andrey, Dimitrov Boyan, Carvalho Ralph, Nygren Anders O H, Boneva Iliana, Mitev Vanyo
Medical University, Department of Chemistry and Biochemistry, 2 Zdrave Street, Sofia 1431, Bulgaria.
BMJ Case Rep. 2009;2009. doi: 10.1136/bcr.06.2008.0139. Epub 2009 May 18.
We report on a fragile X mosaic male full mutation/normal allele detected by PCR and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). This combined analysis provides a diagnostic approach for fragile X syndrome (FXS). The method assesses the presence of expansion (full mutation), the CpG methylation status and could determine copy number changes (large deletions/duplications) along the FMR1 and FMR2 (fragile X mental retardation) genes. The method avoids detection of premutations, which makes it applicable for newborn screening. It can also be used in clarification of mosaic cases. The PCR results in our patient showed one normal allele; three repeats larger than his mother's one. The MS-MLPA showed hypermethylated full mutation pattern in the proband. Both results are compatible with FXS mosaic case full mutation/normal allele. The patient demonstrates atypical mild clinical manifestation of the disease, which correlates to the presence of a normal size allele in the patient's cells.
我们报告了一例通过聚合酶链反应（PCR）和甲基化特异性多重连接依赖探针扩增（MS-MLPA）检测到的脆性X综合征嵌合男性全突变/正常等位基因。这种联合分析为脆性X综合征（FXS）提供了一种诊断方法。该方法可评估扩增（全突变）的存在、CpG甲基化状态，并能确定FMR1和FMR2（脆性X智力低下）基因的拷贝数变化（大片段缺失/重复）。该方法可避免检测到前突变，适用于新生儿筛查。它还可用于明确嵌合病例。我们患者的PCR结果显示一个正常等位基因；三个重复序列比其母亲的大。MS-MLPA显示先证者为高甲基化全突变模式。两个结果均与FXS嵌合病例全突变/正常等位基因相符。该患者表现出该疾病非典型的轻度临床表现，这与患者细胞中存在正常大小的等位基因有关。
