Non‐syndromic skeletal Class III malocclusion is a major craniofacial disorder characterized by genetic and environmental factors. Patients with severe skeletal Class III malocclusion require orthognathic surgery to obtain aesthetic facial appearance and functional occlusion. Recent studies have demonstrated that susceptible chromosomal regions and genetic variants of candidate genes play important roles in the etiology of skeletal Class III malocclusion. Here, we provide a comprehensive review of our current understanding of the genetic factors that affect non‐syndromic skeletal Class III malocclusion, including the patterns of inheritance and multiple genetic approaches. We then summarize the functional studies on related loci and genes using cell biology and animal models, which will help to implement individualized therapeutic interventions.
Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.
ObjectivesTo assess the potential of a radiomics approach of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in the diagnosis of cardiac amyloidosis (CA).Materials and MethodsThis retrospective study included 200 patients with biopsy-proven light-chain (AL) amyloidosis. CA was diagnosed on the basis of systemic amyloidosis confirmed with evidence of cardiac involvement by imaging and clinical biomarkers. A total of 139 patients [54 ± 8 years, 75 (54%) men] in our institution were divided into training cohort [n = 97, mean age of 53 ± 8 years, 54 (56%) men] and internal validation cohort [n = 42, mean age: 56 ± 8 years, 21 (50%) men] with a ratio of 7:3, while 61 patients [mean age: 60 ± 9 years, 42 (69%) men] from the other two institutions were enrolled for external validation. Radiomics features were extracted from global (all short-axis images from base-to-apex) left ventricular (LV) myocardium and three different segments (basal, midventricular, and apex) on short-axis LGE images using the phase-sensitive reconstruction (PSIR) sequence. The Boruta algorithm was used to select the radiomics features. This model was built using the XGBoost algorithm. The two readers performed qualitative and semiquantitative assessment of the LGE images based on the visual LGE patterns, while the quantitative assessment was measured using a dedicated semi-automatic CMR software. The diagnostic performance of the radiomics and other qualitative and quantitative parameters were compared by a receiver operating characteristic (ROC) curve analysis. A correlation between radiomics and the degree of myocardial involvement by amyloidosis was tested.ResultsA total of 1,906 radiomics features were extracted for each LV section. No statistical significance was indicated between any two slices for diagnosing CA, and the highest area under the curve (AUC) was found in basal section {0.92 [95% confidence interval (CI), 0.86–0.97] in the LGE images in the training set, 0.89 (95% CI, 0.79–1.00) in the internal validation set, and 0.92 (95% CI, 0.85–0.99) in the external validation set}, which was superior to the visual assessment and quantitative LGE parameters. Moderate correlations between global or basal radiomics scores (Rad-scores) and Mayo stage in all patients were reported (Spearman’s Rho = 0.61, 0.62; all p < 0.01).ConclusionA radiomics analysis of the LGE images provides incremental information compared with the visual assessment and quantitative parameters on CMR to diagnose CA. Radiomics was moderately correlated with the severity of CA. Further studies are needed to assess the prognostic significance of radiomics in patients with CA.
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