Identification of novel missense mutations associated with non-syndromic syndactyly in two vietnamese trios by whole exome sequencing
| Autor: | Nguyen Dang Ton, Nong Van Hai, Nguyen Thuy Duong, Le Thi Minh Huong, Hoang Hai Duc, Luong Thi Lan Anh, Nguyen Thy Ngoc, Do Hai Quynh |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetics Sanger sequencing Biochemistry (medical) Clinical Biochemistry General Medicine Disease Biology medicine.disease Biochemistry 03 medical and health sciences symbols.namesake 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis GLI3 medicine symbols Missense mutation Syndactyly Exome Exome sequencing Congenital disorder |
| Zdroj: | Clinica Chimica Acta. 506:16-21 |
| ISSN: | 0009-8981 |
| Popis: | Background and methods Syndactyly is a congenital disorder caused by an irregularity in limb formation during the embryonic development. Many studies have demonstrated the critical effect of genetic factor in controlling the outcome of non-syndromic syndactyly. However the signaling pathway causing this disease has not been fully understood. The aim of this study was to identify the genetic mutations that related to syndactyly type I-c and I-d by exome sequencing. Results The exome sequence from two patients revealed two novel heterozygous missense mutations: GLI3: cG1622A pT541M and GJA1: cT274C p.Y92H. Sanger sequencing result confirmed that these mutations were present under heterozygous form in the affected mothers, but not in the unaffected fathers. In-silico analyses by SIFT, Polyphen-2, PredictSNP, PhD-SNP, and PROVEAN did confirm the damaging effect of these mutations in the structure and function of the proteins. Conclusions The result suggested that the two novel mutations may be pathogenic for the disease in these families under the dominant model, provided the initial data for further functional studies to investigate whether those mutations play a disturbing role in the molecular network of syndactyly. |
| Databáze: | OpenAIRE |
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