BackgroundEarly-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening.MethodsIn this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited.ResultsAfter ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis.ConclusionES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

Background Periprosthetic joint infection (PJI) has been increasingly documented; however, its preoperative accurate diagnosis remains challenging. Furthermore, there is a dire need to identify appropriate and effective biomarkers. We aimed to evaluate the relationship between globulin, albumin to globulin (A/G) ratio, and development of PJI in patients undergoing revision total joint arthroplasty (TJA). Methods A retrospective study was conducted on patients who had undergone revision TJA between 2011 and 2018 (89 with aseptic mechanic failure and 38 with PJI). The serum proteins were explored using univariate analysis followed by multivariate logistic regression. The diagnostic performance of these proteins was assessed by the receiver operating characteristic (ROC) curve. Results Higher globulin levels (odds ratio [OR], 1.239; P < 0.001) and lower A/G ratio (OR, 0.007; P < 0.001) were strongly associated with the risk of PJI. ROC curve analysis demonstrated reasonable diagnostic performance for globulin (area under the curve [AUC], 0.77; sensitivity, 78.95%; and specificity, 69.66%) and A/G ratio (AUC, 0.779; sensitivity, 65.79%; and specificity, 78.65%). Conclusions Both globulin and A/G ratio were associated with PJI and may serve as potential adjuvant biomarkers in the diagnosis of PJI.

Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing (ES) data of 523 patients

Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic CS genes remain to be elucidated. In this study, we analyzed exome sequencing (ES) data of 615 Chinese CS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) project. Cosegregation studies for 103 familial CS identified a novel heterozygous nonsense variant, c.2649G>A (p.Trp883Ter) in FBN1. The association between FBN1 and CS was then analyzed by extracting FBN1 variants from ES data of 574 sporadic CS and 828 controls; 30 novel variants were identified and prioritized for further analyses. A mutational burden test showed that the deleterious FBN1 variants were significantly enriched in CS subjects (OR = 3.9, P = 0.03 by Fisher's exact test). One missense variant, c.2613A>C (p.Leu871Phe) was recurrent in two unrelated CS subjects, and in vitro functional experiments for the variant suggest that FBN1 may contribute to CS by upregulating the transforming growth factor beta (TGF-β) signaling. Our study expanded the phenotypic spectrum of FBN1, and provided nove insights into the genetic etiology of CS. Members of the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study are listed below Acknowledgements.

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