ENAM Missense Mutation in Autosomal Recessive Hypoplastic Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) is heterogeneous genetic disorder altering enamel in both primary and permanent dentitions. Hypoplastic AI, thin enamel, usually is inherited as an autosomal dominant (AD) trait; however few cases have been reported with autosomal recessive (AR) inheritance. Enamelin (ENAM), the largest enamel matrix protein, is a glycoprotein shown to be critical for normal enamel formation. Numerous ENAM gene mutations have been reported as having a causative role in AD and AR hypoplastic forms of AI. Objective: To identify a potential ENAM mutation in a newly identified AI proband presenting with generalized hypoplastic enamel and an openbite. Method: The proband was clinically diagnosed with hypoplastic AI at the UAB School of Dentistry. Pedigree information and blood samples from the proband and both parents were collected with IRB approval and informed consent. DNA was extracted from lymphocytes using the Wizard Genomic DNA extraction kit. All ENAM exons and introns borders were amplified by polymerase chain reaction (PCR) using gene specific primers. PCR products underwent bidirectional DNA sequencing reactions. The biological relationship of the parents was confirmed by microsatellite marker analysis. Results: Clinical evaluation revealed the proband was the only affected individual in this six generation family. Both of his parents did not have enamel defects including enamel pitting on oral examine and X-ray analysis. Pedigree analysis showed the parents are third cousins once removed. Sequence analysis revealed the proband had a homozygous missense mutation c.3320G>A, p. S1107N in the ENAM gene with both parents being heterozygous for this allele. This alteration was absent in 86 tested unrelated Caucasian control individuals. Conclusion: Our results support that the alteration c.3320G>A, p.S1107N in ENAM gene is a rare allele in the normal population and that the homozygous mutation in this proband is correlate with his enamel defect. This work supported by IOHR/ UAB-SOD.