Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis
| Autor: | Gulibaha Maimaitili, Jiuxiang Lin, Huizhe Huang, Chong Chen, Huaxiang Zhao, Zulihumaer Nueraihemaiti, Wenbin Huang, Wenjie Zhong, Dilifeire Tuerhong, Yue Zhang, Feng Chen, Qian Zhang, Mengqi Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Patched Medicine (General) endocrine system PTCH1 QH426-470 Biology medicine.disease_cause Biochemistry 03 medical and health sciences R5-920 0302 clinical medicine Genetics medicine Clinical genetics Molecular Biology Gene Genetics (clinical) Exome sequencing Genotype-phenotype analysis Mutation Cell Biology PTCH1 Gene Phenotype Penetrance Cleft lip with or without palate 030104 developmental biology Whole-exome sequencing 030220 oncology & carcinogenesis |
| Zdroj: | Genes and Diseases, Vol 8, Iss 5, Pp 689-697 (2021) |
| ISSN: | 2352-3042 |
| Popis: | The Patched 1 (PTCH1) gene encodes a membrane receptor involved in the Hedgehog (Hh) signaling pathway, an abnormal state of which may result in congenital defects or human tumors. In this study, we conducted whole-exome sequencing on a three-generation Chinese family characterized with variable penetrance of orofacial clefts. A rare heterozygous variant in the PTCH1 gene (c.2833C > T p.R945X) was identified as a disease-associated mutation. Structural modeling revealed a truncation starting from the middle of the second extracellular domain of PTCH1 protein. This may damage its ligand recognition and sterol transportation abilities, thereby affecting the Hh signaling pathway. Biochemical assays indicated that the R945X protein had reduced stability compared to the wild-type in vitro. In addition, we reviewed the locations and mutation types of PTCH1 variants in individuals with clefting phenotypes, and analyzed the associations between clefts and locations or types of variants within PTCH1. Our findings provide further evidence that PTCH1 variants result in orofacial clefts, and contributed to genetic counseling and clinical surveillance in this family. |
| Databáze: | OpenAIRE |
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