| Title | An Analysis of the Pathogenic Genes and Mutation Sites of Macrodactyly |
| Authors | Li, Jian-Feng Tian, Guang-Lei Pan, Hui Zhang, Wen-Tong Li, Da-Cun Liu, Jing-Da Zhao, Liang Li, Hai-Lei |
| Affiliation | Capital Med Univ, Dept Hand Surg, Beijing Shunyi Dist Hosp, 3 Guangming South St, Beijing 101300, Peoples R China Capital Med Univ, Shunyi Teaching Hosp, 3 Guangming South St, Beijing 101300, Peoples R China Peking Univ, Dept Hand Surg, Beijing Jishuitan Hosp, Beijing 100035, Peoples R China Peking Univ, Sch Clin Med 4, Beijing 100035, Peoples R China Capital Med Univ, Dept Pathol, Beijing Shunyi Dist Hosp, Beijing 101300, Peoples R China |
| Keywords | OVERGROWTH PIK3CA PATHWAY |
| Issue Date | 2022 |
| Publisher | PHARMACOGENOMICS & PERSONALIZED MEDICINE |
| Abstract | Objective: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly. Methods: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the wholeexome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes. Results: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p. E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p. G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway. Conclusion: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites. |
| URI | http://hdl.handle.net/20.500.11897/637539 |
| DOI | 10.2147/PGPM.S346373 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京积水潭医院 |
