Amelogenesis imperfecta — Eine Genotyp-Phänotyp-Studie

Abstract

BackgroundAmelogenesis imperfecta (AI) is a hereditary heterogenic developmental disorder of the dental enamel. The diagnosis based on the clinical appearance of the dental enamel. Because of the variability of the phenotype diagnostics might be frequently difficult.AimComparison of the pheno- and genotype of patients with AI. A method for the moleculargenetic diagnostics should be develop to give patients suffered from AI a precise cause related diagnosis and likelihood of repetition.Material and MethodsConcerning the AI 44 members of 17 families were examined. The molecu-largenetic diagnostics was performed in 32 individuals. In advanced 24 individuals were characterized as affected and 8 as not affected. For determination the patient’s genotype venous full-blood was obtained to isolate the DNA followed by the analysis sequencing using of Sanger. The coding region of the known AI causing genes at study start Enamelin (ENAM), Amelogenin (AMELX), Kallikrein-related Pep-tidase 4 (KLK4), Enamelysin (Matrix Metalloprotei-nase 20, MMP20), Distal-less Homeobox 3 (DLX3), WD Repeat-containing Protein 72 (WDR72) und Family with sequence similarity, member H (FAM83H) were completely sequenced.ResultsPathogenic mutations were found in 3 of 7 genes. In three families ENAM-Mutation c.1259_1260insAG, p.(Pro422Valfs*27) occured in homo- or heterozygotes individuals. Characteristics of a generalized hyperplastic AI was verified among homozygotes individuals with this muta -tion. An open bite was present in half of these patients. Two patients were affected by the DLX3-mutation c.561_562delCT, p.(Tyr188Glnfs*13). In 3 siblings from a consanguine family the AI hypo-maturation type was confirmed by the extern performed exon sequencing. Reason was an unknown deletion of the exon 13–18 in the WDR72-gen in the homozygote expression. For 12 AI cases no moleculargenetic diagnosis of the known genes was possible.ConclusionIn concordance with the literature geno-type-phenotype correlations were found in homozygote individuals with ENAM-mutation c.1259_1260insAG, p.(Pro422Valfs*27). The clinical appearance of the individuals with yet unknown WRD72-mutation was consistent with the clinical features described for the AI hypo-maturation type in this gen. Until now further AI causing gens could be identified. Currently 13 gens are known that cause isolated AI forms.