A Novel ENAM mutation in Autosomal Dominant Amelogenesis Imperfecta

Objectives: To develop an efficient strategy for mutational analyses of the molecular genetic etiology of amelogenesis imperfecta, and to identify a mutation in kindred suffering from amelogenesis imperfecta (AI). Methods: Genomic DNA was isolated from peripheral whole blood. Mutational analyses including exons and nearby intron sequences were done for ENAM. PCR amplifications were performed using the HiPi DNA polymerase premix (ElpisBio, Korea). PCR amplification products were purified by the PCR Purification Kit and protocol (ElpisBio, Korea). DNA sequencing was performed at the DNA sequencing center (Macrogen, Korea). Results: Single nucleotide deletion was identified in exon 10 of ENAM gene. According to the nomenclature guidelines for ENAM mutations, this mutation was designated as g.14917delT (c.2991delT). This deletion was predicted to result frameshift, which encodes for 64 novel amino acids and introduce a premature termination at codon 1062 (p.L998fsX1062). The affected mother had hypoplastic horizontal grooves from the middle to the cervical third of the crown, while an affected daughter had wide irregular hypoplastic regions with small hypoplastic spots. Conclusions: Based on a review of the literature, we designed a candidate-gene based mutational analysis strategy that will help clinicians and molecular geneticists determine the genetic etiology of hereditary enamel defects in AI patients. And this strategy revealed a novel ENAM mutation in a new family. This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A060010), the Korea Science and Engineering Foundation (KOSEF) through the Biotechnology R&D program (#2006-05229), and the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-313-E00511).