Tricho-dento-osseous Syndrome Research Articles

A novel DLX3 mutation causes tricho-dento-osseous syndrome with abnormal enamel structure and formation

ObjectiveThis study aimed to identify a DLX3 gene mutation in a family with atypical clinical manifestations of tricho-dento-osseous syndrome (TDO) and its impact on tooth enamel thickness, microhardness, structure and formation. DesignWhole-exome sequencing detected DLX3 mutations in the family. Micro-CT, Vickers hardness tester, energy dispersive spectrometer and scanning electron microscopy were performed on the deciduous teeth of the proband and controls. In vitro experiments preliminarily verified the effect of this mutation on ameloblast differentiation and suggested possible molecular mechanisms. ResultsWe found a new DLX3 frame-shift mutation (NM_005220.3: c.604_605del: p. S202 *) in this family. Compared with control teeth, the mutant enamel showed a significant decrease in thickness, hardness and calcium content and an increase in magnesium content. The enamel structure appeared disordered. In an immortalized ameloblast-lineage cell (ALC) line, this mutation affected ameloblast differentiation and downregulated the expression levels of enamel matrix protein (EMP) genes (Amelx, Tuft1, Klk4, Ambn, Odam). A luciferase reporter assay demonstrated that this mutation significantly reduced the transactivation activity of DLX3 on Amelx/Odam/Klk4. ConclusionWe found a new DLX3 mutation in a Chinese family with enamel dysplasia and that this mutation may affect ameloblast differentiation by inhibiting the transcriptional activity of Amelx/Odam/Klk4, thereby interfering with enamel formation. Our findings further expand the variation spectrum and enrich the evidence of molecular genetics of DLX3 mutations.

Novel DLX3 variant identified in a family with tricho-dento-osseous syndrome

ObjectivesTo identify DLX3 variants in a Chinese family with typical clinical manifestations of tricho-dento-osseous syndrome (TDO). DesignSanger sequencing was performed to detect DLX3 variants in the TDO family. Three-dimensional laser scanning microscopy, bioinformatic and conformational analyses were employed to explore the phenotypic characterization and the functional impact. ResultsWe identified a novel heterozygous variant in the DLX3 gene (c.534G>C; p.Gln178His). Familial co-segregation verified an autosomal dominant inheritance pattern. Bioinformatic prediction demonstrated the deleterious effects of the variant, and DLX3 structure changes suggested the corresponding functional impairments. ConclusionsWe identified a variant in the DLX3 gene in an integrated family of Han nationality for the first time. This study expands the variant spectrum of DLX3 and phenotype spectrum of TDO syndrome.

Tricho-Dento-Osseous Syndrome: A Report of a Familial Cluster and a Literature Review

Tricho-dento-osseous syndrome (TDO), is a very rare, autosomal dominant genetic disorder, commonly characterized by curly hair at infancy, severe enamel hypomineralization and hypoplasia with taurodontism teeth, bone defects and other deformities. Other phenotypic features include flat fingernails and altered craniofacial morphology. A genetic linkage has been identified on chromosome 17q21 in the DLX3 gene. Treatment plan of TDO is to prevent problems such as sensitivity and dental attrition of the hypoplastic structure of the tooth, to promote the esthetics and encourage self-confidence of the patient. In this case report, we present a family with the proband father, and the two children siblings affected by the TDO syndrome. We describe clinical and radiological features, along with dental characteristics and genetic background. Management of TDO syndrome necessitates a multidisciplinary approach, appropriate documentation, and long-term follow up.

UNCOMMON FORM OF ECTODERMAL DYSPLASIA: TRICHO-DENTO-OSSEOUS SYNDROME

<h3>Background</h3> Tricho-dento-osseous syndrome (TDOS) is an autosomal dominant genetic disorder, which is characterized by inherited defects in tissues that arise from epithelial–mesenchymal interaction. The minimal diagnostic criteria for TDOS include enamel hypoplasia, posterior taurodonts, autosomal dominant inheritance pattern, tightly curly hair at birth, and/or radiographic evidence of bone sclerosis. Some authors have questioned whether amelogenesis imperfecta of the hypomaturation–hypoplasia type with taurodontism (AIHHT) and TDOS are distinct conditions or denote a spectrum of the same disease. <h3>Objective(s)</h3> The aim of this study was to increase awareness of TDOS. <h3>Results</h3> A 25-year-old female patient was seeking restorative treatment for the yellowish-brown discoloration of her teeth. Clinical evaluation revealed that she had multiple missing teeth, discolored teeth, frontal bossing, and a concave profile. She was otherwise healthy and not taking any medications. Her medical history indicated a previous diagnosis of ectodermal dysplasia (ED). Panoramic radiography and cone beam computed tomography (CBCT) revealed multiple missing and impacted teeth, as well as retained primary teeth. Reduction in enamel thickness on deciduous and permanent teeth was observed, in addition to taurodont appearance of second permanent molars. Generalized homogeneous ground-glass trabecular pattern in the maxilla and the mandible with a square shape of mandible was noted. <h3>Discussion/Conclusions</h3> In this report, we describe an unusual phenotype of ED, which represents a group of inherited conditions in which 2 or more ectodermally derived anatomic structures fail to develop. TDOS is an uncommon form of ED. The dental findings are clinically similar between TDOS and AIHHT; however, patients with AIHHT lack changes in their hair and bone. In cases where hair, bone, and nail changes are not significant, genetic analysis may help in differential diagnosis. TDOS is genetically linked to markers on chromosome 17 q21.

DLX3 epigenetically regulates odontoblastic differentiation of hDPCs through H19/miR-675 axis

ObjectivesA novel mutation (c.533 A > G; Q178R) in DLX3 gene is responsible for Tricho-Dento-Osseous (TDO) syndrome. As one of features of TDO syndrome is dentin hypoplasia, we explored the mechanism regarding dentin defects in TDO syndrome. DesignhDPCs were obtained from the healthy premolars, stably expressing hDPCs were generated using recombinant lentiviruses. Quantitative methylation analysis, DNMT3B activity, CHIP, and evaluation of odonto-differentiation ability of hDPCs assays were performed. ResultsNovel mutant DLX3 (MU-DLX3) significantly inhibited the expression of long non-coding RNA H19 and resulted in hyper-methylation of H19 in MU group, rescue studies showed that up-regulation the expression of H19 and demethylation of H19 in MU group were able to rescue the effect of MU-DLX3. Subsequently, miR-675, encoded by H19, was also able to rescue the above effects of MU-DLX3. Thus, we proposed that MU-DLX3 regulated odontoblastic differentiation of hDPCs through H19/miR-675 axis. Through CHIP and DNMT3B activity assays disclosed the underlying mechanism by which MU-DLX3 altered H19 expression and methylation status in MU group by increasing H3K9me3 enrichment and DNMT3B activity. ConclusionsOur new findings, for the first time, suggest that MU-DLX3 significantly inhibits hDPCs differentiation via H19/miR-675 axis and provides a new mechanism insight into how MU-DLX3 epigenetically alters H19 methylation status and expression contributes to dentin hypoplasia in TDO syndrome.

MiR-675 promotes odontogenic differentiation of human dental pulp cells by epigenetic regulation of DLX3

In a previous study, we showed that microRNA-675 (miR-675) was significantly down-regulated in patients with tricho-dento-osseous (TDO) syndrome. One of the main features of TDO syndrome is dentin hypoplasia. Thus, we hypothesize that miR-675 plays a role in dentin development. In this study, we determined the role of miR-675 in the odontogenic differentiation of human dental pulp cells (hDPCs). Stable overexpression and knockdown of miR-675 in hDPCs were performed using recombinant lentiviruses containing U6 promoter-driven miR-675 and short hairpin-miR675 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining revealed the promotive effects of miR-675 on the odontogenic differentiation of hDPCs. Further, we found that miR-675 facilitates the odontogenic differentiation process of hDPCs by epigenetic regulation of distal-less homeobox (DLX3). Thus, for the first time, we determined that miR-675 regulates the odontogenic differentiation of hDPCs by inhibiting the DNA methyltransferase 3 beta (DNMT3B)-mediated methylation of DLX3. Our findings uncover an unanticipated regulatory role for miR-675 in the odontogenic differentiation of hDPCs by epigenetic changes in DLX3 and provide novel insight into dentin hypoplasia feature in TDO patients.

DLX3 promotes bone marrow mesenchymal stem cell proliferation through H19/miR-675 axis.

The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis. We found that BMSCs derived from the TDO patient (TDO-BMSCs) had stronger proliferation ability than controls by clonogenic and CCK-8 assays. Next, experiments of overexpression and knockdown of wild-type DLX3 via lentiviruses in normal BMSCs confirmed the results by showing its negative role in cell proliferation. Through validated high-throughput data, we found that the DLX3 mutation reduced the expression of H19 and its coexpression product miR-675 in BMSCs. Function and rescue assays suggested that DLX3, long noncoding RNA H19, and miR-675 are negative factors in modulation of BMSCs proliferation as well as NOMO1 expression. The original higher proliferation rate and the expression of NOMO1 in TDO-BMSCs were suppressed after H19 restoration. Collectively, it indicates that DLX3 regulates BMSCs proliferation through H19/miR-675 axis. Moreover, the increased expression of NOMO1 and decreased H19/miR-675 expression in DLX3 (Q178R) transgenic mice, accompanying with accrual bone mass and density detected by micro-CT, further confirmed our hypothesis. In summary, we, for the first time, demonstrate that DLX3 mutation interferes with bone formation partially through H19/miR-675/NOMO1 axis in TDO syndrome.

DLX3 mutation negatively regulates odontogenic differentiation of human dental pulp cells

ObjectivesThe purpose of this study was to investigate the role of a novel mutant DLX3 on the odontogenic differentiation of human dental pulp cells (hDPCs) in tricho-dento-osseous (TDO) syndrome. DesignhDPCs were obtained from the healthy premolars, stably-expressing wild-type DLX3 (WT), novel mutant DLX3 (Mu) and control vector (NC) cells were generated using recombinant lentiviruses. The proliferation rates of WT-hDPCs and Mu-hDPCs were measured by CCK8 assay. Odonto-differentiation of hDPCs was assessed by alkaline phosphatase (ALP) activity assay, and mineralization ability was assessed by Alizarin red staining. Odontogenic markers, including DMP-1, DSPP, Nes, ALP, and DLX5, were analyzed using real-time polymerase chain reaction (qPCR). DMP-1 and DSPP expressions were further confirmed by Western blotting. ResultsCCK8 results showed that the novel mutant DLX3 decreased the proliferation rate of hDPCs compared with wild-type DLX3. qPCR showed that the novel mutant DLX3 weakened odontogenic differentiation by downregulating the expression of odontogenic genes. These results were further confirmed by Western blotting and ALP activity assay. Additionally, Alizarin red staining showed that the novel mutant DLX3 decreased the mineralization of hDPCs compared with wild-type DLX3. ConclusionsNovel de novo mutation of DLX3 significantly decreases the proliferation rate and inhibits the odontogenic differentiation and mineralization of hDPCs, suggesting that this novel mutation of DLX3 can influence the dentinogenesis in TDO syndrome.

Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

Osteogenesis imperfecta, tricho‐dento‐osseous syndrome and intellectual disability: A familial case with 17q21.33‐q22 (COL1A1 and DLX3) deletion and 7q32.3‐q33 duplication resulting from a reciprocal interchromosomal insertion

We report on a 22-year-old woman with features of osteogenesis imperfecta (OI), tricho-dento-osseous (TDO) syndrome and intellectual disability. Whole genome oligonucleotide microarray analysis revealed a copy number gain of 3 Mb in 7q32.3-q33 and a loss of 3.4 Mb in 17q21.33-q22. FISH analysis showed that the third copy of 7q32 was inserted into the long arm of one chromosome 17, exactly in the region 17q21.33-q22 that was deleted. The maternal uncle presented with clinical features similar to the proposita and had the same chromosomal anomalies. The mother of the proposita and two other family members were balanced carriers of this rearrangement, interpreted as an interchromosomal reciprocal insertion. Reciprocal insertion/four-break rearrangement is a very rare chromosomal event. The deleted region on chromosome 17 contains 39 genes, including COL1A1 and DLX3 involved in OI and TDO syndrome respectively. The CACNA1G gene on the deleted segment of chromosome 17 may be a good candidate gene to explain the intellectual impairment. © 2013 Wiley Periodicals, Inc.

Molecular Consequences of a Frameshifted DLX3 Mutant Leading to Tricho-Dento-Osseous Syndrome

The homeodomain protein Distal-less-3 (Dlx3) plays a crucial role during embryonic development. This transcription factor is known to be essential for placental formation and to be involved in skin and skeletal organogenesis. In humans, a frameshift mutation in the coding sequence of the DLX3 gene results in an ectodermal dysplasia called Tricho-Dento-Osseous syndrome (TDO). The main features of this autosomal dominant disorder are defects in hair, teeth, and bone. To investigate the functional alterations caused by the mutated DLX3(TDO) isoform ex vivo, we used tetracycline-inducible osteoblastic and keratinocyte cell lines and calvarial derived osteoblasts in which the expression of DLX3(WT) and/or DLX3(TDO) could be regulated and monitored. Immunocytochemical analysis revealed that both DLX3(WT) and DLX3(TDO) recombinant proteins are targeted to the nucleus. However, as demonstrated by electrophoresis mobility shift assay, DLX3(TDO) is not able to bind to the canonical Dlx3 binding site. Furthermore, we demonstrate that the frameshifted C-terminal domain in DLX3(TDO) is accountable for the loss of DNA binding activity because the C-terminal domain in DLX3(WT) is not required for DNA binding activity. Although DLX3(TDO) alone cannot bind to a Dlx3 responsive element, when DLX3(WT) and DLX3(TDO) are co-expressed they form a complex that can bind DNA. Concomitant with the inability to bind DNA, DLX3(TDO) has a defective transcriptional activity. Moreover, the transcriptional activity of DLX3(WT) is significantly reduced in the presence of the mutated isoform, indicating that DLX3(TDO) has a dominant negative effect on DLX3(WT) transcriptional activity.

Molecular consequences of a frameshifted Dlx3 mutant leading to Tricho-Dento-Osseous syndrome

The homeodomain protein Distal-less-3 (Dlx3) plays a crucial role during embryonic development. This transcription factor is known to be essential for placental formation and to be involved in skin and skeletal organogenesis. In humans, a frameshift mutation in the coding sequence of the DLX3 gene results in an ectodermal dysplasia called Tricho-Dento-Osseous syndrome (TDO). The main features of this autosomal dominant disorder are defects in hair, teeth, and bone. To investigate the functional alterations caused by the mutated DLX3(TDO) isoform ex vivo, we used tetracycline-inducible osteoblastic and keratinocyte cell lines and calvarial derived osteoblasts in which the expression of DLX3(WT) and/or DLX3(TDO) could be regulated and monitored. Immunocytochemical analysis revealed that both DLX3(WT) and DLX3(TDO) recombinant proteins are targeted to the nucleus. However, as demonstrated by electrophoresis mobility shift assay, DLX3(TDO) is not able to bind to the canonical Dlx3 binding site. Furthermore, we demonstrate that the frameshifted C-terminal domain in DLX3(TDO) is accountable for the loss of DNA binding activity because the C-terminal domain in DLX3(WT) is not required for DNA binding activity. Although DLX3(TDO) alone cannot bind to a Dlx3 responsive element, when DLX3(WT) and DLX3(TDO) are co-expressed they form a complex that can bind DNA. Concomitant with the inability to bind DNA, DLX3(TDO) has a defective transcriptional activity. Moreover, the transcriptional activity of DLX3(WT) is significantly reduced in the presence of the mutated isoform, indicating that DLX3(TDO) has a dominant negative effect on DLX3(WT) transcriptional activity.

DLX3 Mutation in a New Family and Its Phenotypic Variations

Tricho-dento-osseous syndrome (TDO) is an autosomal-dominant disease characterized by curly hair at birth, enamel hypoplasia, taurodontism, and a thick cortical bone. A common DLX3 gene mutation (c.571_574delGGGG) has been identified in multiple families with variable clinical phenotypes. Recently, another DLX3 gene mutation (c.561_562delCT) was reported to cause amelogenesis imperfecta with taurodontism (AIHHT). We identified a Korean family with overlapping phenotypes of TDO and AIHHT. We performed mutational analysis to discover its genetic etiology. The identified mutation was c.561_562delCT mutation in the DLX3 gene. The enamel was hypomature and hypoplastic. The characteristic taurodontic features were not identified. Increased bone density or thickness could not be revealed by cephalometric, hand-wrist, and panoramic radiographs. Affected individuals reported that their nails were brittle, and they had curly hair at birth. This study clearly showed that the c.561_562delCT mutation had not only enamel defects, but also other clinical phenotypes resembling those of TDO syndrome.

DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho‐dento‐osseous syndrome

The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy-terminus of the DLX3 protein is critical in determining its function during development in these different tissues.

Severely hypoplastic amelogenesis imperfecta with taurodontism

The prominent dental feature of a boy was severely hypoplastic enamel in both primary and permanent teeth. Many permanent teeth were already infected while emerging in the oral cavity. Panoramic radiograph showed enlarged and elongated pulp chambers (taurodontism) in the permanent first molars. The clinical and radiological diagnosis was either hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (AIHHT) or tricho-dento-osseous syndrome (TDO). Histological examination of the upper right permanent first molar revealed thin lamellar or somewhat thicker amorphous enamel on approximal surface only with no rods or incremental lines visible. Histologically, the Witkop type AIG designated 'enamel agenesis' cannot be excluded. The medical and dental history of the family members, as well as the boy's medical examination, was noncontributing. He had thick, blond, curly hair. The bone structure of the jaws and skull was normal. For genetic analysis, DLX3 gene was sequenced but no mutation was found. Since the gene defect of TDO has been localized only in the DLX3 gene, the more probable diagnosis was AI.

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.

Increased bone density associated with DLX3 mutation in the tricho-dento-osseous syndrome

Tricho-dento-osseous syndrome (TDO) (OMIM #190320) is an autosomal dominant disorder characterized and named for the three most commonly affected tissues hair, teeth, and bones. Common to all individuals with TDO studied to date is a four base-pair deletion in the DLX3 gene on chromosome 17q21. This mutation is associated with a variable bone phenotype that includes alteration in intramembranous bone formation in the skull. The purpose of this study was to characterize and compare endochondral bone phenotypes and variability at central and peripheral locations of the skeleton by evaluating bone density in individuals having the same DLX3, 4 bp DEL,NT3198 mutation (OMIM 600525) and non-affected family members using dual-energy x-ray absorptiometry (DEXA). Thirty-four individuals (20 TDO-affected and 14 non-affected) participated in this prospective study. All participants were evaluated for the DLX3 mutation associated with TDO. All subjects received DEXA scans at common, literature-supported osteoporotic test regions including: (1) non-dominant distal radius/ulna, (2) femoral neck, and (3) lumbar spine L2–4. There was a significant increase ( P < 0.05) in bone mineral density in TDO-affected individuals compared with control individuals at each test region. The markedly increased bone density in individuals having the DLX3, 4 bp DEL,NT3198 mutation shows that this alteration affects both endochondral and intramembranous bone formation and suggests that the DLX3 gene is important in bone formation and/or homeostasis of the appendicular skeleton.

Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions.

Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) is inherited as a highly penetrant autosomal dominant trait. These dental findings are similar to those of another autosomal dominant condition, the tricho-dento-osseous syndrome (TDO), from which AIHHT differs primarily by lack of changes in the hair and bones. TDO is characterized by a highly variable clinical phenotype. While enamel hypoplasia and taurodontism appear to be present in all TDO cases, non-dental features may be absent, with approximately half of TDO cases losing the kinky/curly hair phenotype seen in infancy by adolescence, and in almost 20% of cases, osseous changes are not evident. The genetic basis for AIHHT is unknown and it has been questioned whether AIHHT and TDO are separate conditions or a spectrum of disease. The genetic basis for TDO has recently been identified as a deletion mutation in the distal-less 3 (DLX3) transcription factor gene. To determine if AIHHT and TDO represent variable expression of a common DLX3 gene mutation, allelic mutations of the DLX3 gene, or mutations in DLX7 (the linked paralogue to DLX3 on chromosome 17), we have performed mutational analysis and sequencing studies of the DLX3 and DLX7 genes in three individuals (two affected and one unaffected) from a family with AIHHT. Results of the analysis demonstrate that AIHHT and TDO are not due to a common DLX3 gene mutation. Sequence analyses of the DLX3 and DLX7 genes suggest AIHHT is not due to genetic mutations or polymorphisms in the exons of these genes. These results suggest that AI-HHT and TDO are two genetically distinct conditions.

A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families.

Tricho-dento-osseous syndrome (TDO) is characterised by a variable clinical phenotype primarily affecting the hair, teeth, and bone. Different clinical features are observed between and within TDO families. It is not...

Enamel Structure and Composition in the Tricho-Dento-Osseous Syndrome

Tricho-dento-osseous syndrome (TDO) is an autosomal dominant disorder characterized by curly hair, hypoplastic enamel, taurodontism, and dense bone. The purpose of this investigation was to characterize the enamel defects in a TDO population in North Carolina. Twelve TDO teeth and 12 normal teeth were examined. The enamel thickness was decreased in all TDO teeth ranging from having no enamel to about 60% the thickness of normal teeth. Half of the TDO teeth had primarily prismless enamel while the remainder had at least occasional areas of prismatic enamel. TDO enamel crystallites appeared similar to normal crystallites with TEM. The mineral per volume of TDO enamel (n =9) (68.5%) was significantly less, on average, compared with normal enamel (n=8) (84.5). The genetic mutation responsible for the TDO phenotype results in alteration of a developmental pathway(s) common to hair, teeth and bone. This further illustrates that these embryologically diverse tissues share common developmental controls at the molecular level.