A Novel Missense Mutation in the EDAR Gene and One Missense Mutation in EDA Gene in the Study of HED Patients in Iran

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia that is the result of faulty ectodermal development leading to such ectodermal defects as hypotrichosis, anodontia or hypodontia, and hypohidrosis or anhidrosis. Xlinked HED is caused by mutations in ectodysplasin A (EDA) gene and accounts for 90% of all HED cases. Autosomal HED is caused by mutations in other involved genes, such as EDA-receptor (EDAR) gene. In this study, we included two distinct families with three HED patients. We collected 5 mL of peripheral blood from the probands, associated parents, and 120 matched unrelated controls (from related ethnicity) without any ectodermal disorder. DNA was extracted using the routine salting-out protocol from blood leukocytes. Polymerase chain reaction (PCR) purification and bidirectional Sanger sequencing of the PCR products were performed. We identified p.R156H (c.467 G > A) mutation in EDA gene in two affected brothers and their carrier mother (family 1) and a novel missense mutation c.1210G > A (p.A404T) in EDAR gene in a 4-year-old affected boy and his heterogeneous parents (family 2). Clinical evaluation, genetic findings, and bioinformatic analysis supported deleterious effects of both identified mutations on the EDA and EDAR gene products, which should be considered in genetic assessment of HED cases in Southwest of Iran.