Bartholdi D, Klein A, Weissert M, Koenig N, Baumer A, Boltshauser E, Schinzel A, Berger W, Mátyás G
Institute of Medical Genetics, University of Zurich, Schwerzenbach.
Clin Genet. 2006 Apr;69(4):319-26. doi: 10.1111/j.1399-0004.2006.00604.x.
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG binding protein 2 (MeCP2). Recently, a new isoform of MeCP2 including exon 1 was identified. This new isoform is more abundantly expressed in brain than the isoform including exons 2-4. Very little is known about the phenotypes associated with mutations in exon 1 of MECP2 since only a limited number of RTT patients carrying such mutations have been identified so far. In this study, we screened a cohort of 20 girls with RTT for exon 1 mutations by sequencing and multiplex ligation-dependent probe amplification (MLPA). We identified one girl with a novel exon 1 mutation (c.30delCinsGA) by sequencing and three with genomic rearrangements by MLPA. Comparison of the phenotypes showed that the girls carrying a mutation or rearrangement encompassing exon 1 were more severely affected than the girls with rearrangements not affecting exon 1.
瑞特综合征（RTT）是一种神经发育障碍疾病，由编码甲基化CpG结合蛋白2（MeCP2）的X连锁MECP2基因突变引起。最近，一种包含外显子1的MeCP2新亚型被鉴定出来。这种新亚型在大脑中的表达比包含外显子2 - 4的亚型更为丰富。由于迄今为止仅鉴定出有限数量携带此类突变的RTT患者，因此对于与MECP2外显子1突变相关的表型了解甚少。在本研究中，我们通过测序和多重连接依赖探针扩增（MLPA）对20名RTT女孩队列进行了外显子1突变筛查。通过测序我们鉴定出一名携带新型外显子1突变（c.30delCinsGA）的女孩，通过MLPA鉴定出三名有基因组重排的女孩。表型比较显示，携带包含外显子1的突变或重排的女孩比未影响外显子1的重排女孩受影响更严重。
