Novel Mutations in ED1 in Families with hypohidrotic ectodermal dysplasia

Objective: X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the ectodermal dysplasias characterized by an abnormal development of hair, teeth and sweat (MIM 305100). The estimated incidence of the disease is about 1 per 100,000 births. The ED1 gene responsible for the disorder encodes a protein, ectodysplasin-A, is a member of the tumor necrosis factor superfamily of ligands. Recently, various mutations of the gene have been detected in the disease, but to date few studies have been carried in Asian, especially in Chinese. The purpose of this study is to detect gene mutation in X-linked hypohidrotic ectodermal dysplasia in Chinese families.

Methods: Five unrelated Chinese families affected with hypohidrotic ectodermal dysplasia were recruited for this study. Each patient has typical symptoms of XLHED, including sever tooth agenesis in both primary and permanent dentition. Peripheral blood samples were obtained from the family members. Genomic DNA was extracted. Polymerase chain reaction, direct sequencing and restriction enzyme reaction were performed to identify the mutations.

Results: Mutations were identified in ED1 gene in each family: C412G, A1201G, C1375T and 1124-1127Del 4bp. Two of these mutations have not been previously reported, which change the transmembrane domain and TNF-like domain of the protein respectively. The same mutation, C1375T, was identified in two different families.

Conclusion: Our finding indicates that mutations in the ED1 gene were responsible for the phenotypes of the hypohidrotic ectodermal dysplasia in the Chinese families. Despite the different character and localization of the mutations, no apparent correlation between phenotype and genotype of the patients was evidenced. The detection of these mutations could be applied in prenatal diagnosis for the families.