Sant Joan de Déu Research Foundation, Barcelona, Spain.
Sant Joan de Déu Research Institute (IRSJD), Hospital Sant Joan de Déu, Esplugues de Lobregat (Barcelona), Spain.
Mol Genet Genomic Med. 2019 Aug;7(8):e793. doi: 10.1002/mgg3.793. Epub 2019 Jun 17.
Rett syndrome (RTT) is a developmental disorder with an early onset and X-linked dominant inheritance pattern. It is first recognized in infancy and is seen almost always in girls, but it may be seen in boys on rare occasions. Typical RTT is caused by de novo mutations of the gene MECP2 (OMIM300005), and atypical forms of RTT can be caused by mutations of the CDKL5 (OMIM300203) and FOXG1 (OMIM*164874) genes.
Approximately 5% of the mutations detected in MECP2 are large rearrangements that range from exons to the entire gene. Here, we have characterized the deletions detected by multiplex ligation-dependent probe amplification (MLPA) in the gene MECP2 of 21 RTT patients. Breakpoints were delineated by DNA-qPCR until the amplification of the deleted allele by long-PCR was possible.
This methodology enabled us to characterize deletions ranging from 1,235 bp to 85 kb, confirming the partial or total deletion of the MECP2 gene in all these patients. Additionally, our cases support the evidence claiming that most of these breakpoints occur in some restricted regions of the MECP2 gene.
These molecular data together with the clinical information enable us to propose a genotype-phenotype correlation, which is essential for providing genetic counseling.
雷特综合征（RTT）是一种起病早、X 连锁显性遗传的发育障碍。它在婴儿期首次被发现，几乎只发生在女孩中，但在极少数情况下也可能发生在男孩中。典型的 RTT 是由 MECP2 基因（OMIM300005）的新生突变引起的，而不典型的 RTT 可能由 CDKL5（OMIM300203）和 FOXG1（OMIM*164874）基因突变引起。
在 MECP2 中检测到的大约 5%的突变是从外显子到整个基因的大片段重排。在这里，我们对 21 例 RTT 患者的基因 MECP2 中通过多重连接依赖性探针扩增（MLPA）检测到的缺失进行了特征描述。通过 DNA-qPCR 对断点进行描绘，直到可以通过长 PCR 扩增缺失等位基因。
这种方法使我们能够对 1,235 bp 到 85 kb 范围内的缺失进行特征描述，证实了所有这些患者的 MECP2 基因的部分或完全缺失。此外，我们的病例支持了大多数这些断点发生在 MECP2 基因的一些限制区域的证据。
这些分子数据结合临床信息，使我们能够提出一种基因型-表型相关性，这对于提供遗传咨询至关重要。
