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Abstract：
Fragile X syndrome (FXS) [OMIM 300624] is a common X-linked inherited syndrome with an incidence only second to that of trisomy 21. More than 95% of fragile X syndrome is caused by reduced or absent fragile X intellectual disability protein 1 (FMRP) synthesis due to dynamic mutation expansion of the CGG triplet repeat in the 5\'UTR and abnormal methylation of the FMR1 (fragile X messenger ribonucleoprotein 1) gene [OMIM 309550]. Less than 5% of cases are caused by abnormal function of the FMRP due to point mutations or deletions in the FMR1 gene. In a proband with clinical suspicion of FXS and no CGG duplication, we found the presence of c.585_586del (p.Lys195AsnfsTer8) in exon 7 of the FMR1 gene using whole exome sequencing (WES). This variant resulted in frameshift and a premature stop codon after 8 aberrant amino acids. This variant is a novel pathogenic mutation, as determined by pedigree analysis, which has not been reported in any database or literature.
摘要：
脆性X综合征（FXS）[OMIM300624]是一种常见的X连锁遗传综合征，其发病率仅次于21三体。超过95％的脆性X综合征是由于5'UTR中CGG三联体重复的动态突变扩展和FMR1（脆性X信使核糖核蛋白1）基因[OMIM309550]的异常甲基化导致的脆性X智力障碍蛋白1（FMRP）合成减少或缺失。少于5%的病例是由于FMR1基因中的点突变或缺失导致的FMRP功能异常引起的。在临床怀疑FXS且无CGG重复的先证者中，我们发现c.585_586del的存在（p。Lys195AsnfsTer8）使用全外显子组测序（WES）在FMR1基因的外显子7中。该变体在8个异常氨基酸后导致移码和过早终止密码子。这种变异是一种新的致病突变,根据谱系分析确定，尚未在任何数据库或文献中报告。
