Abstract：
BACKGROUND: Fragile X syndrome (FXS) is mainly caused by FMR1 CGG repeat expansions. Other types of mutations, particularly deletions, are also responsible for FXS phenotypes, however these mutations are often missed by routine clinical testing.
METHODS: Molecular diagnosis in cases of suspected FXS was a combination of PCR and Southern blot. Measurement of the FMRP protein level was useful for detecting potentially deleterious impact.
RESULTS: PCR analysis and Southern blot revealed a case with premutation and suspected deletion alleles. Sanger sequencing showed that the deletion involved 313 bp upstream of repeats and some parts of CGG repeat tract, leaving transcription start site. FMRP was detected in 5.5 % of blood lymphocytes.
CONCLUSIONS: According to our review of case reports, most patients carrying microdeletion and full mutation had typical features of FXS. To our knowledge, our case is the first to describe mosaicism of a premutation and microdeletion in the FMR1 gene. The patient was probably protected from the effects of the deletion by mosaicism with premutation allele, leading to milder phenotype. It is thus important to consider appropriate techniques for detecting FMR1 variants other than repeat expansions which cannot be detected by routine FXS diagnosis.
METHODS: Molecular diagnosis in cases of suspected FXS was a combination of PCR and Southern blot. Measurement of the FMRP protein level was useful for detecting potentially deleterious impact.
RESULTS: PCR analysis and Southern blot revealed a case with premutation and suspected deletion alleles. Sanger sequencing showed that the deletion involved 313 bp upstream of repeats and some parts of CGG repeat tract, leaving transcription start site. FMRP was detected in 5.5 % of blood lymphocytes.
CONCLUSIONS: According to our review of case reports, most patients carrying microdeletion and full mutation had typical features of FXS. To our knowledge, our case is the first to describe mosaicism of a premutation and microdeletion in the FMR1 gene. The patient was probably protected from the effects of the deletion by mosaicism with premutation allele, leading to milder phenotype. It is thus important to consider appropriate techniques for detecting FMR1 variants other than repeat expansions which cannot be detected by routine FXS diagnosis.
摘要：
背景：脆性X综合征（FXS）主要由FMR1CGG重复扩增引起。其他类型的突变,特别是删除，也负责FXS表型，然而，这些突变通常被常规的临床试验所遗漏。
方法：疑似FXS病例的分子诊断是PCR和Southern印迹的结合。FMRP蛋白水平的测量可用于检测潜在的有害影响。
结果：PCR分析和Southern印迹显示一例具有前突变和疑似缺失等位基因。Sanger测序显示，缺失涉及CGG重复序列上游313bp和部分重复序列，离开转录起始位点。在5.5%的血液淋巴细胞中检测到FMRP。
结论：根据以前FMR1微缺失病例的回顾，大多数同时缺失和完全突变的患者具有典型的FXS临床特征.据我们所知,我们的案例首次描述了FMR1基因的前突变和微缺失的镶嵌性.患者可能通过带有前突变等位基因的镶嵌性来保护其免受缺失的影响，导致更温和的表型。因此,重要的是考虑用于检测FMR1变体的适当技术,而不是常规FXS诊断不能检测到的重复扩增。
方法：疑似FXS病例的分子诊断是PCR和Southern印迹的结合。FMRP蛋白水平的测量可用于检测潜在的有害影响。
结果：PCR分析和Southern印迹显示一例具有前突变和疑似缺失等位基因。Sanger测序显示，缺失涉及CGG重复序列上游313bp和部分重复序列，离开转录起始位点。在5.5%的血液淋巴细胞中检测到FMRP。
结论：根据以前FMR1微缺失病例的回顾，大多数同时缺失和完全突变的患者具有典型的FXS临床特征.据我们所知,我们的案例首次描述了FMR1基因的前突变和微缺失的镶嵌性.患者可能通过带有前突变等位基因的镶嵌性来保护其免受缺失的影响，导致更温和的表型。因此,重要的是考虑用于检测FMR1变体的适当技术,而不是常规FXS诊断不能检测到的重复扩增。
