Novel ITGB6 mutation in autosomal recessive amelogenesis imperfecta.

OBJECTIVE: Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell-cell and cell-extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation. MATERIALS AND METHODS: We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology. RESULTS: Autozygosity mapping and exome sequencing identified a novel homozygous ITGB6 transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the ßI-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars. CONCLUSIONS: In this study, we identified a novel homozygous ITGB6 mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development.

Does enamelin have pleiotropic effects on organs other than the teeth? Lessons from a phenotyping screen of two enamelin-mutant mouse lines.

We analyzed two mutant mouse lines, ATE1 and ATE2, that carry point mutations in the enamelin gene which result in premature stop codons in exon 8 and exon 7, respectively. Both mutant lines show amelogenesis imperfecta. To establish the effect of mutations within the enamelin gene on different organs, we performed a systematic, standardized phenotypic analysis of both mutant lines in the German Mouse Clinic. In addition to the initially characterized tooth phenotype that is present in both mutant lines, we detected effects of enamelin mutations on bone and energy metabolism, as well as on clinical chemical and hematological parameters. These data raise the hypothesis that enamelin defects have pleiotropic effects on organs other than the teeth.

A rare association--amelogenesis imperfecta, platispondyly and bicytopenia: a case report.

INTRODUCTION: Amelogenesis imperfecta is an inherited disease characterized by generalized structural abnormalities of the enamel on all teeth, including both primary and permanent dentition. To the best of our knowledge, this is the first case report of a rare association of amelogenesis imperfecta, platyspondyly, and bicytopenia. CASE PRESENTATION: A 5-year-old Moroccan boy was examined in the Centre for Dental Consultation and Treatment, Faculty of Dentistry, Rabat. He was a child of consanguineous parents (first degree). The child failed to thrive (-4 standard deviation score) and displayed delayed overall development. A dental examination revealed a hypoplastic amelogenesis imperfecta with a bacterial biofilm deposit on tooth surfaces. A complete blood count revealed bicytopenia (normocytic-normochromic anemia with thrombocytopenia). A radiographic examination of the spinal column showed a deviation of the spine in the frontal plane in the form of thoracolumbar scoliosis. The interpedicular distance was not expanded; but a mild platyspondyly exists, especially pronounced in T11 and T12. CONCLUSIONS: No other family members presented amelogenesis imperfecta, bicytopenia, or platyspondyly. The consanguineous marriage suggested an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect producing this syndrome, and the symptomatic associations of amelogenesis imperfecta, platyspondyly and bicytopenia.