Mutations In The ED1 Gene Of X-linked Hypohidrotic Ectodermal Dysplasia

Background Hypohidrotic ectodermal dysplasia(HED)which is found worldwide with an estimated incidence of 1 per 100000 births is a monogenic inherited disease of skin characterized by the ectodermal hypoplasia of sweat glands,hair and teeth et. The typical clinical manifestation is hypohidrosis/ anhidrosis,sparse/scanty hair and absent teeth or tooth that are malformed.The facial appearance consists of a prominent foread, a flattened bridge of the nose,thick lips,and dark-colored skin around the eyes.The disease has genetic heterogeneity.Most cases are caused by mutations in the ED1 gene on Xq12-13.1,which are inherited in an X-linked recessive pattern.ED1 gene encodes a protein,ectodysplasin-A(EDA),recognized to be a member of the numor necrosis factor(TNF) superfamily of ligands.Ectodysplasin-A is involved in the regulation of ectodermal morphogenesis.To date,above 80 mutations in the ED1 gene have been included in homo-sapiens gene bank,including missense mutations, nonsense mutations, splice junction mutations,small deletion/insertion mutations and large deletion or molecular transposition.Of these,missense mutations are 50. Comparison between genotype and phenotype failed to yield any clear correlation between the nature of the mutation and the clinical features of XLHED. In the present study, we have ascertained two Chinese families with XLHED, and examined ED1 gene mutations in these two families by direct sequencing.Mutation analysis in families with XLHED allows for genetic counselling,prenatal diagnosis and gene therapy.Objective To identify pathogenic mutations of the ED1 gene in two Chinese pedigrees with XLHED. Methods We collected two Chinese families and their blood samples. Genomic DNA was extracted from peripheral blood.8 coding exons and their flanking sequences of ED1 were amplified by polymerase chain reaction and products analyzed by direct sequencing.Results We identified two mutations including one novel frameshift(c.952delG)and one missense(c.1045A>G)which has been previously reported in ED1. The probands'mothers was heterozygote with wild and mutant types at the same nucleotide position. The mutations was not detected in probands'fathers and 100 normal controls. These results suggested that the mutations of ED1 are not rare polymorphism.Conclusions Our data suggests that these two mutations in the ED1 gene could cause XLHED in Chinese Han population.At the same time,we add new variants to the repertoire of ED1 mutations in XLHED,and that is useful for genetic counselling,carrier detection and prenatal diagnosis in XLHED families.