Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

Amelogenesis imperfecta: genotype-phenotype studies in 71 families.

Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified.

Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate.

A consanguineous Arab pedigree in which recessive amelogenesis imperfecta (AI) and cone-rod dystrophy cosegregate, was screened for linkage to known retinal dystrophy and tooth abnormality loci by genotyping neighbouring microsatellite markers. This analysis resulted in linkage with a maximum lod score of 7.03 to the marker D2S2187 at the achromatopsia locus on chromosome 2q11, and haplotype analysis placed the gene(s) involved in a 2 cM/5 Mb interval between markers D2S2209 and D2S373. The CNGA3 gene, known to be involved in achromatopsia, lies in this interval but thorough analysis of its coding sequence revealed no mutation. Furthermore, affected individuals in four consanguineous recessive pedigrees with AI but without CRD were heterozygous at this locus, excluding it as a common cause of non-syndromic recessive AI. It remains to be established whether this pedigree is segregating two closely linked mutations causing disparate phenotypes or whether a single defect is causing pathology in both teeth and eyes.

Oral focal mucinosis: report of 15 cases and review of the literature.

AIMS: To describe 15 cases of oral focal mucinosis (OFM) and compare these to previously reported cases. METHODS: Cases diagnosed as OFM in the period 1981-2003-were reviewed. Clinical information provided at the time of submission of each specimen was retrieved and supplemented by additional clinical details provided by the respective clinician at the time of compilation of this paper. The literature was reviewed. RESULTS: OFM presented as an innocuous soft tissue swelling that may be either pedunculated or sessile. The gingiva was confirmed as the most common site for OFM, with a predominance of females affected. Microscopically, OFM is characterised by an area of myxoid tissue which is usually well-defined. The lesion is periodic acid-Schiff (PAS)-negative and alcian blue-positive, with pre-digestion with hyaluronidase preventing the alcian blue staining. As the differential diagnosis includes myxoid neural lesions, S100 staining is important in establishing the diagnosis, with cases of OFM being negative. CONCLUSIONS: The cause of OFM remains unknown. The cases presented in this paper bring OFM to the attention of anatomical pathologists when considering the differential diagnosis of myxoid lesions of the oral cavity.

Enamel defects and Lyonization in focal dermal hypoplasia.

We report a pattern of enamel hypoplasia in focal dermal hypoplasia similar to that found in females with X-linked amelogenesis imperfecta. Three cases of focal dermal hypoplasia are described, with specific focus on the oral and dental features. In these cases the teeth all had vertical grooving with notching of the incisal or cuspal tips. Also recorded were blunt roots of taurodont form with open apices and missing teeth in 1 case. Oral papillomas were present in 2 cases. The pattern of enamel defects is attributed to Lyonization, which is consistent with the pattern of skin and bone lesions typically seen in focal dermal hypoplasia. This supports the proposal that focal dermal hypoplasia is X-linked. The authors conclude that the pattern of dental defects in focal dermal hypoplasia is consistent with Lyonization.

Dental findings in a family with hyperparathyroidism-jaw tumor syndrome and a novel HRPT2 gene mutation.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an important diagnosis because of the possible involvement of other family members and risk of malignant disease. We report clinical and genetic studies in a previously undocumented Australian family with HPT-JT. The proband and his sister presented with bilateral or recurrent mandibular radiolucencies diagnosed histopathologically as cemento-ossifying fibromas. Mutation screening of the recently identified disease gene HRPT2 was performed by direct sequencing in 3 affected members. This revealed a novel mutation in exon 1 of HRPT2 (nt 20AGGACG --> GGGAG), which is predicted to inactivate the parafibromin protein through protein truncation and premature termination of translation. The terminology used for the jaw lesions in this syndrome warrants review to become more consistent. Cemento-ossifying fibroma is the preferred term to better reflect the pathologies found in most individuals and families,and to emphasize the significance of the jaw lesions in the diagnosis of the syndrome.

DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism.

Amelogenesis imperfecta hypoplastic-hypomaturation with taurodontism (AIHHT) is an autosomal dominant (AD) trait associated with enamel defects and enlarged pulp chambers. In this study, we mapped an AIHHT family to human chromosome 17 q21-q22 (lod score 3.3) and identify a two basepair deletion (CT) at nucleotide 560 in DLX3 associated with the disease. This mutation causes a frameshift altering the last two amino acids of the DNA-binding homeodomain introducing a premature stop codon truncating the protein by 88 amino acids. This is the first report of a mutation within the homeodomain of DLX3. Previous studies have shown a DLX3 mutation outside the homeodomain associated with tricho-dento-osseous syndrome (TDO) suggesting TDO and some forms of AIHHT are allelic.

Oral medicine and oral pathology--the impact of electronic information.

This paper discusses recent advances in electronic information, with particular reference to Oral Medicine and Oral Pathology. Email has become the norm for professional communication; Medline is freely accessible; content alerts can be established to alert the subscriber to new publications; evidence-based practice is emerging with the development of the Cochrane library and numerous other databases are also available for a variety of purposes. Conferences are moving to use electronic information as the medium for dissemination of proceedings. Bulletin boards provide a forum for interchange of ideas and opinions in both Oral Medicine and Oral Pathology and electronic data transfer can be used in various applications in telemedicine, telepathology and teleradiology. Without doubt these mechanisms will be further developed and refined in the present century.

Odontogenic cyst with verrucous proliferation.

An unusual case of an odontogenic cyst with verrucous proliferation is described in a 13-year-old girl. This histologically distinctive odontogenic cyst variant does not appear to have been reported previously. The cyst was characterised by a series of verrucous projections in the lumen with hypergranulosis and cells resembling koilocytes, raising the possibility of a viral aetiology. However, no evidence of human papillomavirus (HPV) was found using immunohistochemistry and polymerase chain reaction (PCR) amplification.