Jin Pengzhen, Yan Kai, Ye Shaofen, Qian Yeqing, Wu Zaigui, Wang Miaomiao, Xu Yuqing, Xu Yanfei, Dong Minyue
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, China.
Front Genet. 2021 Nov 19;12:772958. doi: 10.3389/fgene.2021.772958. eCollection 2021.
Synonymous mutations are generally considered non-pathogenic because it did not alter the amino acids of the encoded protein. Publications of the associations between synonymous mutations and abnormal splicing have increased recently, however, not much observations available described the synonymous mutations at the non-canonical splicing sites leading to abnormal splicing. In this pedigree, the proband was diagnosed Neurofibromatosis type I due to the presence of typical cafe' au lait macules and pectus carinatum. Whole-exome sequencing identified a synonymous mutation c.6795C > T (p.N2265N) of the gene which was located at the non-canonical splicing sites. Reverse transcription polymerase chain reaction followed by Sanger sequencing was carried out, and the skipping of exon 45 was observed. Therefore, the pathogenicity of the synonymous mutation c.6795C > T was confirmed. Our finding expanded the spectrum of pathogenic mutations in Neurofibromatosis type I and provided information for genetic counseling.
同义突变通常被认为是非致病性的，因为它不会改变编码蛋白质的氨基酸。然而，最近关于同义突变与异常剪接之间关联的出版物有所增加，但没有太多观察结果描述非经典剪接位点处导致异常剪接的同义突变。在这个家系中，先证者因存在典型的牛奶咖啡斑和鸡胸而被诊断为I型神经纤维瘤病。全外显子测序在该基因位于非经典剪接位点处鉴定出一个同义突变c.6795C>T（p.N2265N）。进行了逆转录聚合酶链反应，随后进行桑格测序，观察到外显子45的跳跃。因此，同义突变c.6795C>T的致病性得到了证实。我们的发现扩展了I型神经纤维瘤病致病突变的谱，并为遗传咨询提供了信息。
