Novel missense mutation in the EDA gene in a family affected by oligodontia.

BACKGROUND: Mutations in the EDA-EDAR-EDARADD genes and more recently, mutations in the WNT10A gene have been described as the cause of syndromic and nonsyndromic tooth agenesis concomitant with diverse abnormalities of ectodermally derived tissues. AIM: In the present investigation, two brothers presenting severe tooth agenesis (oligodontia) concomitant with subtle signs of ectodermal dysplasia (ED) symptoms, as well as six family relatives were analyzed for a causative mutation. METHODS: Genomic DNA was isolated from saliva, and genetic screening performed via direct sequencing of PCR fragments covering the entire coding regions and the intron-exon junctions of the EDA, EDAR, EDARADD as well as the WNT10A genes. Mutation analysis was conducted using the Mutation Surveyor(®) Software. RESULTS AND CONCLUSION: We identified a novel G > A mutation located on exon 7 at nucleotide position c.866 in the EDA gene in both patients. The nucleotide change results in a substitution of arginine by histidine (p.Arg289His). According to the programs MutationTaster and PolyPhen2, this mutation is pathogenic. Based on a computerized protein structure analysis, we suggest that the change p.Arg289His in EDA impairs protein stabilization and thus might possibly be involved in the development of oligodontia concomitant with a mild ED phenotype.