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Abstract：
Fragile X syndrome (FXS) is caused by CGG-repeat expansion in the 5\' UTR of FMR1 of >200 repeats. Rarely, FXS is caused by deletions; however, it is not clear whether deletions including only the non-coding region of FMR1 are pathogenic. We report a deletion in the 5\' UTR of FMR1 in an unaffected male infant and review 12 reported deletions involving only the non-coding region of FMR1. Genetic testing was requested in a male infant born to a mother harbouring a FMR1 full mutation. The maternal grandmother carried a FMR1 premutation. FMR1 CGG repeats were analysed using repeat-primed PCR. Only a short PCR fragment was amplified and subsequent Sanger sequencing detected an 88 bp deletion in hemizygous form. The deletion included all CGG repeats and flanking sequences but no FMR1 exons. Linkage analysis using STR markers revealed that the deletion had occurred on the allele, which was expanded in the mother and the maternal grandmother. Reverse transcription and quantitative PCR showed normal FMR1 mRNA levels. Grønskov et al. reported a 157 bp deletion of all CGG repeats and flanking sequences in a female without FXS hemizygous for the FMR1 gene due to a deletion on the other X chromosome. Protein expression was unaffected by the deletion. The reported deletion comprises the deletion detected in the male infant. At almost 2 years of age he is unaffected. Based on these observations and the normal FMR1 mRNA level, we conclude that a spontaneous rescue of an FMR1 repeat expansion has occurred.
摘要：
脆性X综合征(FXS)是由CGG-重复序列在FMR1的5'UTR中扩增>200个重复序列引起的。很少,FXS是由删除引起的;然而,尚不清楚仅包括FMR1非编码区的缺失是否致病.我们报告了一个未受影响的男婴的FMR1的5'UTR缺失，并回顾了12个报告的仅涉及FMR1非编码区的缺失。在母亲具有FMR1全突变的男性婴儿中要求进行基因检测。外祖母进行了FMR1预突变。使用重复引发的PCR分析FMR1CGG重复。仅扩增了短的PCR片段，随后的Sanger测序检测到半合子形式的88bp缺失。缺失包括所有CGG重复和侧翼序列,但没有FMR1外显子。使用STR标记的连锁分析显示缺失发生在等位基因上，在母亲和外祖母中进行了扩展。逆转录和定量PCR显示正常的FMR1mRNA水平。Grønskov等人。报道了由于另一个X染色体上的缺失，FMR1基因没有FXS半合子的雌性中所有CGG重复序列和侧翼序列的157bp缺失。蛋白质表达不受缺失的影响。所报告的缺失包括在男婴中检测到的缺失。在将近2岁的时候，他没有受到影响。基于这些观察和正常的FMR1mRNA水平，我们得出的结论是,FMR1重复扩张的自发抢救已经发生.
