Search Results (357)

Objective: Several studies have compared the accuracy of digital scans and conventional impressions for post space capture. However, only a few have specifically investigated the precision of intraoral scanners in measuring post spaces of varied lengths. This study aimed to evaluate the accuracy of various intraoral scanning techniques in capturing long and short post spaces. Material and Methods: This study grouped samples into eight categories based on four techniques and two post space depths (7 and 11 mm). After tooth preparation, root canal treatment, and post space preparation, laboratory scans were performed using Duralay. Intraoral scans were obtained directly and indirectly with the Trios fourth generation scanner using the Duralay and PVS techniques. The accuracies, in terms of trueness, and precisions were compared after ten repetitions for each group using the Kruskal–Wallis or Mann–Whitney U tests. Results: The Duralay Intraoral Scan groups demonstrated a high consistency, while the Direct Intraoral Scan groups showed moderate consistency. Variability was higher for the Duralay Lab Scan and PVS Intraoral Scan groups for short post spaces. Conclusions: The capture technique significantly affected the accuracies of the post space measurements. The techniques also demonstrated varying consistency and precision. These findings provide critical insights to guide their selections for clinical and research applications. Clinical Significance: This study is one of the few to compare the accuracy of intraoral scanners for the capture of both short and long post spaces. It addresses a key gap in current dental research and offers practical guidance for clinicians and researchers in selecting appropriate scanning techniques for various clinical scenarios. The findings have the potential to enhance the accuracy and reliability of post space measurements and improve patient outcomes. Full article

This in vitro study aims to compare the trueness of digital impressions obtained using two intraoral scanners (IOS) and one photogrammetry device for full-arch implant-supported rehabilitations. According to the Caramês Classification I, three models were produced with Straumann implants arranged in different spatial distributions: Option A with six implants and Options B and C with four implants each. The three models were scanned using a 12-megapixel scanner to create digital master casts. For each reference model, 30 digital impressions were acquired: 10 with the 3Shape Trios 3 intraoral scanner, 10 with the Medit i500 intraoral scanner, and 10 with the PIC Dental photogrammetry device. Trueness was assessed through best-fit superimpositions between the digital master casts and the corresponding virtual models. The Shapiro–Wilk test was applied to assess the normality of the data distribution, and Levene’s test was used to evaluate the homogeneity of variances. The non-parametric Kruskal–Wallis test was employed to compare group differences, with post hoc adjustments made using the Bonferroni correction. A significance threshold of p = 0.05 was adopted for all statistical tests. Statistically significant differences were observed in the root mean square values among the three devices. The Medit i500 demonstrated the highest trueness, with a median (interquartile range) deviation of 24.45 (18.18) µm, whereas the PIC Dental exhibited the lowest trueness, with a median deviation of 49.45 (9.17) µm. Among the implant distribution, the Option C showed the best trueness, with a median deviation of 19.00 (27.83). Considering the results of this in vitro study, intraoral scanners demonstrated comparable trueness, whereas the photogrammetry-based system exhibited lower trueness values. Additionally, a smaller number of implants and reduced inter-implant distances were associated with improved trueness in digital impressions for full-arch implant rehabilitation. Full article

This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances. Hormonal evaluations confirmed primary adrenocortical insufficiency, necessitating ongoing hydrocortisone and fludrocortisone therapy. Using family trio-based amplicon sequencing of the CYP21A2 gene, we identified compound heterozygosity consisting of a full gene deletion and a novel pathogenic intronic mutation. Additionally, analysis of WGS data was performed to rule out pathogenic variants in genes that might lead to a similar phenotype, thereby eliminating the possibility of other genes contributing to the proband’s disease. This case demonstrates the potential of using amplicon sequencing in molecular genetic diagnostic testing to detect rare intronic variants in the CYP21A2 gene in cases of early-onset adrenal failure. It also contributes to a better understanding of the genetic basis of congenital adrenal hyperplasia (CAH), which remains a significant autosomal recessive disorder affecting cortisol and aldosterone production, with an incidence of 1 in 10,000 to 1 in 15,000 globally. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as DPH1, DPH2, and DPH5, result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in DPH5, encoding a methyltransferase required for diphthamide synthesis. Methods: Clinical, neurological, and dysmorphological evaluations were performed by a multidisciplinary team. Brain MRI was acquired on a 3T scanner. Craniofacial abnormalities were assessed using the GestaltMatcher phenotyping tool. Whole exome sequencing (WES) was conducted on leukocyte-derived DNA with a trio-based approach. Bioinformatic analyses included variant annotation, filtering, and pathogenicity prediction using established databases and tools. Results: The affected subject carried a previously reported missense change, p.His260Arg, suggesting the occurrence of genotype–phenotype correlations and a hypomorphic behavior of the variant, likely explaining the overall milder phenotype compared to the previously reported patients with DPH5-related diphthamide deficiency syndrome. Conclusions: Overall, the co-occurrence of short stature, relative macrocephaly, congenital heart defects, variable DD/ID, minor skeletal and ectodermal features, and consistent craniofacial features suggests a differential diagnosis with Noonan syndrome and related phenotypes. Full article

Background: The increasing adoption of digital workflows in implant dentistry necessitates rigorous assessment of intraoral scanning, particularly for complex full-arch rehabilitations like All-on-Four prostheses, where posterior implant angulation may impact the accuracy of optical data acquisition. Objectives: This in vitro study aimed to assess the accuracy of digital intraoral scanners in scanning All-on-Four implant models with different posterior implant angulations. Methods: Two epoxy resin All-on-Four implant models were fabricated with two posterior implant angulations (30-degree and 45-degree). Both models were digitized to obtain control datasets using a Smart Optics reference scanner (REF). Four intraoral scanners were comparatively assessed: Cerec Omnicam AC (OMN), Trios 4 (TRI), Cerec Primescan AC (PRI), and Medit i700 (MED), with nine scans per each scanner (n = 9). All STL files were exported and analyzed using Geomagic Control X with root mean square (RMS) values computed for trueness and precision assessments. Results: The comparison between IOS types in terms of trueness revealed that with 30° angulation, the MED group showed the statistically significant least deviation (p = 402). With 45° angulation, both PRI and OMN scanners showed the statistically significant highest deviation values (p = 0.047 and 0.007, respectively). MED again showed the statistically significant least deviation (p = 402). For precision evaluation in 30° angulation models, PRI and OMN scanners showed the statistically significant least deviation values (p = 402 and <0.001, respectively). While, in 45° angulation models, no statistically significant inter-scanner differences were observed. Conclusions: While MED, PRI, and OMN scanners demonstrated clinical validity for 30° angled posterior implants, only the MED system achieved sufficient accuracy for 45° tilt. These findings emphasize the critical relationship between scanner selection and extreme implant angulations in full-arch digital workflows. Full article

Dysregulated expression of nuclear receptor superfamily 4 group A member 2 (NR4A2) has recently been associated with autistic spectrum disorder (ASD), speech impairment, and neurodevelopmental delay (NDD); however, its precise role in the prevalence and etiopathogenesis of ASD has not been fully elucidated. Herein, we aimed to explore the role of NR4A2 variants in the genetic underpinnings of ASD among Saudi children of different age ranges and phenotype severities. A total of 338 children with ASD from 315 unrelated families (293 simplex, 2 quads, and 1 quintet) were screened for NR4A2 variants via exome sequencing (ES) of the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs), after which the probands with identified NR4A2 variants were further subjected to trio genetic analyses. ES analysis revealed 10 de novo NR4A2 variants (5 indels/nonsense, 2 missense, and 3 variants affecting splicing) in 8 unrelated probands (2.37%) and 2 affected siblings from 8 unrelated families (6 simplex (2.04%) and 2 quads (8.7%)). Three NR4A2 variants were notably recurrent among both affected and unaffected carriers. All identified indels and two splicing variants met the criteria for pathogenic/loss-of-function (LoF) variants according to the ACMG classification (PVS1), whereas the missense variants were classified as of uncertain significance (VUS). This study is among the first to identify such a high frequency of recurrent variants in an ASD cohort, suggesting their significant contribution to the etiopathogenesis of ASD within this population. Full article

The spectrin family genes play critical roles in cytoskeletal organization and cellular integrity, yet their evolutionary and functional significance in non-classical model organisms remains poorly explored. Here, we systematically identified and characterized spectrin family genes in the silkworm Bombyx mori. Genome-wide analysis identified 17 predicted spectrin genes, which were integrated into eight optimized members through transcriptome-guided structural refinement. Multi-species genomic analysis revealed 8, 23, and 24 spectrin family genes in Drosophila melanogaster, Mus musculus, and Homo sapiens, respectively. Phylogenetic analysis revealed conserved clades across insects and mammals, with gene family expansions in vertebrates. Spatiotemporal expression profiling demonstrated ubiquitous expression of these genes during silkworm development. Population genomic analyses detected strong selection signatures in BmTrio during domestication and implicated BmBeta_spc as a candidate gene for silk yield enhancement in Chinese-improved strains (CHN-I). Expression profiles of parental strains and F₁ offspring from a commercial hybrid cross (Jingsong × Haoyue) revealed BmBeta_spc expression correlating with heterosis in silk yield traits. This study elucidates the characterization and functional relevance of silkworm spectrin genes, providing insights into their roles in domestication and breeding. Full article

CSMD1 is a gene involved in various biological processes and is highly expressed in the central nervous system, where it plays a key role in complement activity, brain circuit development, and cognitive function. It has been implicated as a susceptibility gene for schizophrenia and a causative factor in developmental epileptic encephalopathy, neurodevelopmental disorders, and intellectual disability. However, no MIM phenotype number has been assigned to CSMD1 for a specific disorder. Here, we report an individual presenting with moderate intellectual disability, anxiety disorder, obsessive–compulsive personality traits, and facial dysmorphisms. Trio-based whole-exome sequencing (WES) identified two heterozygous CSMD1 variants, c.8095A>G and c.5315T>C, both classified as variants of uncertain significance (VUS) according to ACMG criteria. Computational analysis using the DOMINO tool supported an autosomal recessive inheritance model for CSMD1. This study contributes to the growing evidence linking CSMD1 to neurodevelopmental phenotypes, highlighting the need for further investigations to clarify its pathogenic role. Full article

Primary osteoporosis in children and young adults often suggests a monogenic disease affecting bone microarchitecture and bone mineral density. While Osteogenesis Imperfecta (OI) is the most recognized genetic cause of recurrent fractures, many other genes involved in bone metabolism may contribute to osteoporosis. Among them, FGFR2 plays a critical role in bone growth and development by regulating osteoblast differentiation and proliferation, as well as chondrogenesis. Germline pathogenic FGFR2 variants are typically associated with syndromic craniosynostosis, conditions not characterized by bone fragility or osteoporosis. A report recently identified FGFR2 as a potential cause of dominant early-onset osteoporosis and bone fractures in a family. We report the case of a child affected by severe osteoporosis with multiple fractures. We performed clinical exome sequencing in trio to investigate potential genetic causes of the observed phenotype and identified a likely mosaic pathogenic FGFR2 variant, absent in both parental samples. Our findings provide further evidence that FGFR2 pathogenic variants can lead to a novel non-syndromic bone mineralization disorder, reinforcing the role of FGFR2 in the pathogenesis of early-onset osteoporosis. Full article

Objectives: The objective of this study was to examine changes in facial soft tissue asymmetry over time in patients after Class II orthognathic surgery using three-dimensional (3D) stereophotogrammetry. Methods: The study consists of 54 patients with a skeletal Class II malocclusion (32 female, 22 male; mean age, 33.2 years). Three-dimensional photographic data were collected using the 3dMD Trio stereophotogrammetry system. The evaluation of 21 anthropometric landmark positions was conducted before surgery (T0), 6 months (T1), and 12 months (T2) after surgery. Facial asymmetry was classified as mild (0–2 mm), moderate (3–5 mm), or severe (>5 mm). Results: There was a small difference in the mean distance when analyzing the asymmetry of the whole face. The 3D measurements showed statistically significant differences (p < 0.05) between T0 versus T1 and T2 time-point values. Prior to surgery, males exhibited a higher degree of soft tissue asymmetry compared to females. The chin volume asymmetry score was higher in the females of the cohort and patients undergoing bimaxillary surgery (median 1.11) than in the males of the cohort and patients undergoing single-jaw surgery (median 1.08); however, these differences were not statistically different. Conclusions: The findings indicate that soft tissue asymmetry may become altered within a 6-month period following surgery. Full article

Background: Uniparental disomy (UPD) is the inheritance of both copies of a chromosome from a single parent, leading to distinct genetic conditions. Maternal UPD of chromosome 6 (UPD(6)mat) is extremely rare, with few molecularly confirmed cases reported. Methods: We report a prematurely born female with isodisomic UPD(6)mat, presenting with intrauterine growth restriction (IUGR), developmental delay, autism spectrum disorder, dysmorphic features, and a sacrococcygeal teratoma. In addition, we reviewed 24 confirmed UPD(6)mat cases to assess clinical patterns in prenatal findings, birth outcomes, and postnatal features. Results: Trio whole-exome sequencing revealed complete isodisomy of chromosome 6 and a de novo heterozygous DIAPH2 variant of uncertain significance. In the literature review, IUGR was present in 87% of cases, with most individuals born small for gestational age and preterm. Failure to thrive and neurodevelopmental issues were also frequent. While the exact molecular basis remains unknown, imprinting disturbances—similar to those in UPD(6)pat—and cryptic trisomy 6 mosaicism, particularly in heterodisomy, are the most likely mechanisms. No specific gene or consistent epigenetic abnormality has been identified. Conclusions: This study aims to enhance the understanding of the genetic and phenotypic spectrum of UPD(6)mat, improving diagnostic and management approaches for this ultra-rare genetic disorder. We propose a detailed list of clinical assessments and tests to be performed following the detection of maternal uniparental disomy of chromosome 6. Full article

Background: Digital impression techniques for edentulous patients present unique challenges due to the absence of stable anatomical landmarks and variable soft tissue morphology. While intraoral scanners have shown promising results in dentate patients, their application in edentulous cases remains problematic, with reported accuracy deviations ranging from 60.6 ± 11.9 μm to 67.2 ± 6.9 μm compared to conventional methods. Material and Methods: This pilot study employed a within-subject, repeated-measures design comparing four scanning protocols in a fully edentulous patient (age: 42, BMI: 24.3 kg/m², Cawood and Howell Class III). Digital scans were performed using iTero Element 5D and Trios 5 scanners (n = 10 scans per group), with and without a modified technique incorporating standardized reference points (1 mm diameter, 5 mm intervals) and systematic soft tissue management. A conventional impression-derived digital model served as the reference standard. Accuracy assessment utilized best-fit alignment and root mean square (RMS) calculations through Geomagic Control X software (version 2020.1.1). Results: The modified technique demonstrated significantly improved accuracy (Groups C/D: 57.8–59.7 μm) compared to standard protocols (Groups A/B: 66.9–68.2 μm) (p < 0.001). Mean scanning times were reduced by 37% with the modified technique (2:10 ± 0:09 min vs. 3:24 ± 0:15 min). Inter-operator reliability showed excellent agreement (ICC = 0.92, 95% CI: 0.88–0.95). Soft tissue management significantly improved vestibular area accuracy (48.7 ± 6.3 μm vs. 72.4 ± 8.9 μm, p < 0.001). Conclusions: The proposed scanning strategy incorporating reference points and systematic soft tissue management significantly improved both accuracy and efficiency in digital impressions of edentulous arches. The technique showed excellent reproducibility and potential clinical applicability across different scanner systems. These findings warrant validation through larger-scale clinical trials to establish definitive protocols for digital impression-taking in edentulous patients. Full article

Phosphatidylinositol glycan class T (PIGT) is part of the glycosylphosphatidylinositol transamidase (GPI-TA) complex, crucial for various cell functions. Biallelic pathogenic variants in PIGT are associated with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), a rare neonatal hypotonia syndrome characterized by dysmorphic features and seizures. Diagnosing neonatal hypotonia, which has diverse congenital and acquired causes, is challenging, particularly in syndromic monogenic cases. Next-generation sequencing is essential for accurate diagnosis. This study reports a term newborn with hypotonia, dysmorphic features, seizures, and severe skeletal issues, including a humeral fracture at birth, consistent with MCAHS3. Trio whole exome sequencing (WES) analysis revealed a novel homozygous missense variant in PIGT, expanding the clinical spectrum of MCAHS3 and marking the first such case in the Thai population. The identified c.257A>G (p.His86Arg) variant manifests a severe MCAHS3 phenotype, as evidenced by reduced CD59 expression in western blot analysis, indicating impaired GPI-AP synthesis. Computational predictions suggest this mutation causes protein instability, potentially affecting GPI anchor attachment. While alkaline phosphatase (ALP), a GPI-AP crucial for skeletal mineralization, was elevated in this case, suggesting a late-stage GPI synthesis defect. The His86Arg mutation in PIGT may disrupt GPI-TA function, hindering proper protein attachment and leading to cleaved protein secretion. Further functional studies are needed to elucidate the impact of this mutation on PIGT function and MCAHS3 phenotypes. Full article

This trio-based whole-genome sequencing (WGS) study enhances the accuracy of variant detection by leveraging parental genotypes, which facilitates the identification of de novo mutations and population-specific variants. Nonetheless, the comprehensive genetic variation data of the Thai population remain limited, posing challenges to advancing personalized medicine and population-based screening strategies. We establish the genetic variation information of a healthy Thai population by analyzing the sequences of 40 trios, yielding 120 whole genomes (excluding offspring). The resulting dataset encompasses 20.2 million variants, including 1.1 million novel and 19.1 million known variants. Within this dataset, we identify 169 pathogenic variants, of which 56 are classified as rare and 87 are absent from the ClinVar database as of version 2023. These pathogenic variants, particularly the rare and de novo mutations, will likely be of significant interest for genetic association studies. Notably, one pathogenic variant linked to a de novo mutation is found in the SF3B2 gene, which is associated with craniofacial microsomia. With its innovative methodology and comprehensive dataset, our trio-based whole-genome sequencing study provides an invaluable representation of the genetic variations in the Thai population. These data provide a critical foundation for further analyses of the pathogenic variants related to human disease phenotypes in genetic association studies. Full article

Background: This study aims to compare treatment time and patient satisfaction between digital and conventional impression techniques in single-tooth implant prosthetics. Materials and Methods: A controlled study was conducted on 22 patients with single-tooth loss in the posterior arch who underwent implant replacement. Impressions were taken using both conventional techniques (polyvinyl siloxane) and digital methods (3Shape Trios 3 Move scanner). Results: The digital impression technique significantly reduced treatment time compared to the conventional method. The total procedure time and individual steps in the digital process were notably shorter than those in the conventional process (p < 0.001). Patients who underwent digital impressions reported not only significantly higher satisfaction and comfort levels but also less pain, unpleasant taste, and level of nausea (p < 0.001). Conclusions: Digital impressions can be superior in reducing treatment time and improving patient satisfaction compared to conventional methods, highlighting their advantages in single-tooth implant prosthetics. However, further research, involving different digital systems and clinical evaluations, is required to fully validate these advantages. Full article