Identification and functional analysis of a novel missense mutation Ser250Phe underlying congenital coagulation factor Ⅶ deficiency

Abstract

To analyze GJB6 gene mutations in a Chinese family with hidrotic ectodermal dysplasia and to provide first-trimester prenatal diagnosis for a fetus. Mutation scanning was carried out with PCR and bilateral direct sequencing in 2 affected and 6 unaffected individuals from the family. After the mutation was confirmed, prenatal diagnosis was performed on chorionic villi samples obtained at 11th gestational week. A heterozygous missense mutation c.31G>A of the GJB6 gene was discovered in all of the patients, which has led to substitution of glycine by arginine at codon 11 (p.G11R) at the N-terminal of the GJB6 protein. Prenatal diagnosis indicated that the fetus had also carried the same p.G11R mutation. Following termination of the pregnancy, analysis of the aborted tissues was consistent with prenatal diagnosis. The missense mutation c.31G>A(p.G11R) of the GJB6 gene probably underlies the disease in this family. Prenatal diagnosis with DNA sequencing can facilitate genetic counseling of this family.