Yelda Kasimoglu

Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.

Condylar asymmetry in different occlusion types.

Abstract Aims: The purpose of this study was to investigate the relationship between vertical asymmetries of the mandibular condyle with different occlusion types, including Angle Cl I, Cl II, Cl III malocclusions and unilateral posterior crossbite (UPC) in adolescent patients. Methodology: A total number of 120 patients (60 girls, 60 boys with a mean age of 13·64±1·58 years) with no signs and symptoms of temporomandibular disorders were included in the study [n = 30 for each group; Group I: normal occlusion, Group II: Angle Class II malocclusion, Group III: Angle Class III malocclusion and Group IV: UPC]. The asymmetry index for each patient was measured using panoramic radiographs. The results were analyzed using Kruskal–Wallis and Mann–Whitney U test at the 95% confidence level. Results: The results of the analyses showed no statistically significant differences between the gender and the age of the patients for condylar height asymmetry (P>0·05). No statistically significant difference was found between the occlusion types, according to condylar asymmetry level. The patients with UPC showed a significantly different level of condylar height asymmetry compared to the Class I, II and III occlusion types (P<0·05; P<0·01). Conclusions: Patients with UPC have asymmetric condylar heights. These patients might be at risk for developing skeletal mandibular asymmetries in the future. Early correction of posterior crossbite can help practitioners prevent skeletal asymmetries.

Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

OBJECTIVE To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). SUBJECTS AND METHODS DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. RESULTS Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The probands mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. CONCLUSIONS In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes.

The dentin phosphoprotein repeat region and inherited defects of dentin

Nonsyndromic dentin defects classified as type II dentin dysplasia and types II and III dentinogenesis imperfecta are caused by mutations in DSPP (dentin sialophosphoprotein). Most reported disease‐causing DSPP mutations occur within the repetitive DPP (dentin phosphoprotein) coding sequence. We characterized the DPP sequences of five probands with inherited dentin defects using single molecule real‐time (SMRT) DNA sequencing. Eight of the 10 sequences matched previously reported DPP length haplotypes and two were novel. Alignment with known DPP sequences showed 32 indels arranged in 36 different patterns. Sixteen of the 32 indels were not represented in more than one haplotype. The 25 haplotypes with confirmed indels were aligned to generate a tree that describes how the length variations might have evolved. Some indels were independently generated in multiple lines. A previously reported disease‐causing DSPP mutation in Family 1 was confirmed and its position clarified (c.3135delC; p.Ser1045Argfs*269). A novel frameshift mutation (c.3504_3508dup; p.Asp1170Alafs*146) caused the dentin defects in Family 2. A COL1A2 (c.2027G>A or p.Gly676Asp) missense mutation, discovered by whole‐exome sequencing, caused the dentin defects in Family 3. We conclude that SMRT sequencing characterizes the DPP repeat region without cloning and can improve our understanding of normal and pathological length variations in DSPP alleles.

Rethinking isolated cleft lip and palate as a syndrome

OBJECTIVE The goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts. STUDY DESIGN We studied 1573 DNA samples combining individuals that were born with CL/P or had tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries with the goal to identify genetic associations. We tested 2 single-nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Overrepresentation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an α of .05. RESULTS We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of the conditions described earlier. When subgroups were tested, associations were found for individuals with hypomineralization. CONCLUSIONS Although we did not test this hypothesis directly in the present study, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition, and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care.

Investigation of the Er: YAG laser and diamond bur cavity preparation on the marginal microleakage of Class V cavities restored with different flowable composites: TUNA et al.

The purpose of this study was to evaluate the efficiency of the Er:YAG laser and diamond bur cavity preparation on the marginal microleakage of Class V cavities. Group 1: bur preparation (bp) + Vertise Flow (VF); Group 2: laser preparation (lp) + VF; Group 3: bp + Adper Easy One (AEO) + Filtek Ultimate Flowable Composite (FUFC); Group 4: lp + AEO + FUFC; Group 5: bp + Clearfil S3 Bond (CSB) + Clearfil Majesty Flow (CMF); Group 6: lp + CSB + CMF. Data were analyzed by Kruskal–Wallis and Mann–Whitney U tests (p < .05). More microleakage was observed in cervical regions compared to occlusal regions in all groups (p < .05). No significant difference was observed among all groups in terms of occlusal and cervical surfaces, respectively (p > .05). The use of the Er:YAG laser for cavity preparation with different adhesive systems and flowable composites did not influence microleakage.

Management of dental anxiety in children using robots

Anxiety related to dental treatment is a common case in children and causes serious problems. In this study, we proposed a novel technique based on the use of a humanoid robot companion to improve the childs experience in the clinicall environment by minimizing pain and anxiety during a dental procedure. Thus, we designed and developed a human-robot interaction scenario with children in the range of 4-to-10 years old. We presented an experimental setup involving a humanoid robot that enabled a Wizard of Oz experiment. We assessed the performance of the proposed system by using questionnaires applied to patients and dentists, as well as by measuring the pulse rates of the patients.

Preservation of Involved Teeth Associated with Large Dentigerous Cysts

Dentigerous cysts (DCs) are benign odontogenic cysts that are associated with the crowns of permanent teeth. The purpose of this study is to describe the management of DCs in four children. Four boys aged between 7 and 9 years were referred to our clinics with the complaints of intraoral alveolar swelling or facial asymmetry on the affected area. The panoramic radiographies showed large, well-defined radiolucent lesions associated with the deciduous teeth and displaced tooth buds. The treatment consisted of the extraction of the involved deciduous tooth and marsupialization of the cyst to allow eruption of the permanent tooth. Permanent teeth displaced by the DCs in three cases erupted spontaneously within one-year period. The case with horizontally displaced permanent tooth was managed by replantation. This is the first time that underlying permanent tooth in a DC case was intentionally replanted.

Hypoplastic AI with Highly Variable Expressivity Caused by ENAM Mutations

Tooth enamel, the hardest tissue in the human body, is formed after a complex series of interactions between dental epithelial tissue and the underlying ectomesenchyme. Nonsyndromic amelogenesis imperfecta (AI) is a rare genetic disorder affecting tooth enamel without other nonoral symptoms. In this study, we identified 2 novel ENAM mutations in 2 families with hypoplastic AI by whole exome sequencing. Family 1 had a heterozygous splicing donor site mutation in intron 4, NM_031889; c.123+2T>G. Affected individuals had hypoplastic enamel with or without the characteristic horizontal hypoplastic grooves in some teeth. Family 2 had a nonsense mutation in the last exon, c.1842C>G, p.(Tyr614*), that was predicted to truncate the protein by 500 amino acids. Participating individuals had at least 1 mutant allele, while the proband had a homozygous mutation. Most interestingly, the clinical phenotype of the individuals harboring the heterozygous mutation varied from a lack of penetrance to a mild hypoplastic enamel defect. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations.

Prevalence and characteristics of talon cusps in Turkish population

Background: Talon cusp is a rare dental anomaly characterized by a cusp-like projection, often including the palatal surface of the affected tooth. The aim of the present study was to investigate the prevalence and characteristics of talon cusps in a group of Turkish children. Materials and Methods: The study population consisted of 14,400 subjects who attended the clinics of the Department of Pediatric Dentistry at the Istanbul University, Istanbul, Turkey. Subjects ranged in age from 1 to 14 years with a mean age of 10.5 ± 2.55 years. Talon cusps were mainly categorized by visual examination according to the classification of Hattab et al. The distribution and frequency of talon cusps were calculated with respect to dentition type, tooth type, talon type, the affected surface, associated dental anomalies, and clinical complications. Statistical analysis included descriptive statistics, frequencies, and crosstabs with Chi-square analysis. Results: Talon cusps were detected in 49 subjects (26 males and 23 females) of 14,400 (0.34%). A total of 108 teeth showed talon cusps. Distribution of talon cusps according to gender showed no statistically significant differences. The incidence of talon cusps was found to be greater in maxillary lateral incisors (53.7%) than central incisors (29.62%). Regarding the type of talon cusp, 47.22% of teeth showed a Type III talon cusp, whereas 30.55% of teeth demonstrated a Type II talon and 22.22% of teeth demonstrated a Type I talon cusp. Nine patients (18.36%) with talon cups also exhibited other developmental dental anomalies. Clinical complications associated with talon cusps were detected as caries formation and occlusal interference. Conclusion: This is the most comprehensive study of the prevalence of talon cusps in Turkish population using the largest sample size to date. Also, taurodontism associated with a talon cusp has been reported here for the 1st time. Clinical complications associated with talon cusps need more investigations.