3.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.

Object The object of this study was to assess the feasibility and efficacy of a novel, minimally invasive spinal surgery technique to correct degenerative lumbar spinal stenosis involving a modified unilateral-approach microendoscopic midline decompression. Methods In this prospective study, 41 patients with lumbar stenosis were randomly assigned to undergo either a novel, median-approach microendoscopic laminectomy (20 patients) or a conventional laminectomy (21 patients). Spinal anteroposterior diameter, cross-sectional area, lateral recess distance, spinal stability, postoperative back pain, functional outcomes, and muscle trauma were evaluated. Follow-up ranged from 16 to 24 months, with a mean of 17.8 months for the novel procedure group and 18.6 months for the conventional laminectomy group. Results Compared with patients in the conventional laminectomy group, patients who received the novel procedure had a reduced mean duration of hospital stay, a lower mean creatine phosphokinase muscular-type isoenzyme level, a lower visual analog scale score for back pain at 1-year follow-up, and a faster recovery rate. These patients also had less mean blood loss compared with the conventionally treated group. Satisfactory neurological decompression and symptom relief were achieved in 90% of these patients. There was no significant clinical difference compared with the conventional laminectomy group's results. There was no evidence of spinal instability in any patient, and no patient required a follow-up conventional laminectomy. Conclusions This novel procedure provides effective spinal decompression. Although this method requires more operating time than a conventional method, it requires only minimal muscle trauma and spinal stability maintenance, and allows for early mobilization. This shortens the hospital stay, reduces postoperative back pain, and leads to satisfactory neurological and functional outcomes. Moreover, with the midline approach, decompression was accomplished without compromising the facet joints, even with a narrow width of lamina.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis -expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

Progression of degeneration of cervical spine on MRI was frequently observed during 10-year period, with development of symptoms in 34% of subjects. No factor related to progression of degeneration of cervical spine was identified except for age.