| Autor: |
Defu Lin, Huakang Du, Sen Zhao, Bowen Liu, Hongcheng Song, Guannan Wang, Weiping Zhang, Haiyan Liang, Pei Liu, Chao Liu, Wenwen Han, Zhenwu Li, Yang Yang, Shuofan Chen, Lina Zhao, Xiaoxin Li, Zhihong Wu, DISCO (Deciphering Disorders Involving Scoliosis & COmorbidities) study group, Ning Sun, Nan Wu |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Orphanet Journal of Rare Diseases, Vol 17, Iss 1, Pp 1-10 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1750-1172 |
| DOI: |
10.1186/s13023-022-02334-5 |
| Popis: |
Abstract Background Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias. Results A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias. Conclusion Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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