Nguyen Thy Ngoc1, Nguyen Thuy Duong2, Do Hai Quynh3, Nguyen Dang Ton2, Hoang Hai Duc4, Le Thi Minh Huong4, Luong Thi Lan Anh5, Nong Van Hai2. 1. Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Viet Nam; University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Viet Nam. Electronic address: nguyen-thy.ngoc@usth.edu.vn. 2. Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Viet Nam; Institute of Genome Research, Vietnam Academy of Science and Technology, Viet Nam. 3. Institute of Genome Research, Vietnam Academy of Science and Technology, Viet Nam. 4. Vietnam National Children's Hospital, Viet Nam. 5. Genetic Counseling Center, Hanoi Medical University Hospital, Hanoi Medical University, Viet Nam.
Abstract
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.
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.