Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amelogenesis imperfecta (AI) is an inherited tooth disorder affecting tooth enamel formation only. A gene for autosomal dominant AI, the local hypoplastic form, has been localized to a 4 Mb region on chromosome 4q (AIH2). The enamelin gene (ENAM ), has been mapped to chromosome 4q21, to the same region as AIH2, and was recently shown to be mutated in patients with smooth and thin hypoplastic autosomal dominant AI (ADAI). In this study, we describe an ENAM mutation causing the local hypoplastic form of ADAI, a phenotype that accounts for 27% of the autosomally inherited cases in Northern Sweden. This nonsense mutation in the enamelin gene results in a truncated peptide of 52 amino acids as compared with 1142 amino acids of the normal protein. Our results show that while a splice site mutation is associated with smooth and thin hypoplastic AI, a base substitution resulting in a shorter peptide causes local hypoplasia of the enamel, a milder form of AI. These findings support ENAM as a disease gene, and shed new light on the molecular mechanism of the disease and to the function of the enamelin protein in enamel formation.
Hum Mol Genet 2002 May 01
PMID:A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2). 1197 66

Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.
Hum Mol Genet 2005 Mar 01
PMID:Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI). 1564 48