Dataset Information

Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

ABSTRACT:

Background

Early-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.

Methods

In 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.

Results

After 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.

Conclusion

ES 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.

SUBMITTER: Zhao S

PROVIDER: S-EPMC7802082 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

Zhao Sen S Zhang Yuanqiang Y Chen Weisheng W Li Weiyu W Wang Shengru S Wang Lianlei L Zhao Yanxue Y Lin Mao M Ye Yongyu Y Lin Jiachen J Zheng Yu Y Liu Jiaqi J Zhao Hengqiang H Yan Zihui Z Yang Yongxin Y Huang Yingzhao Y Lin Guanfeng G Chen Zefu Z Zhang Zhen Z Liu Sen S Jin Lichao L Wang Zhaoyang Z Chen Jingdan J Niu Yuchen Y Li Xiaoxin X Wu Yong Y Wang Yipeng Y Du Renqian R Gao Na N Zhao Hong H Yang Ying Y Liu Ying Y Tian Ye Y Li Wenli W Zhao Yu Y Liu Jia J Yu Bin B Zhang Na N Yu Keyi K Yang Xu X Li Shugang S Xu Yuan Y Hu Jianhua J Liu Zhe Z Shen Jianxiong J Zhang Shuyang S Su Jianzhong J Khanshour Anas M AM Kidane Yared H YH Ramo Brandon B Rios Jonathan J JJ Liu Pengfei P Sutton V Reid VR Posey Jennifer E JE Wu Zhihong Z Qiu Guixing G Wise Carol A CA Zhang Feng F Lupski James R JR Zhang Jianguo J Wu Nan N

Journal of medical genetics 20200507 1

<h4>Background</h4>Early-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.<h4>Methods</h4>In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and th ...[more]

PMID: 32381727

Similar Datasets

Project description:BackgroundChêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60 degrees showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently.MethodsThe patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60 degrees thoracic and 59 degrees lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13 degrees thoracic and 13 degrees lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche.ResultsAfter a treatment time of 27 Month the Cobb angle increased to 74 degrees thoracic and 65 degrees lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26 degrees thoracic and 28 degrees lumbar to 30 degrees thoracic and 28 degrees lumbar. The ATR improved to 12 degrees thoracic and 5 degrees lumbar while Lateral deviation improved from 22.4 mm to 4.6 mm and average surface rotation improved from 10.6 degrees to 6 degrees. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result.ConclusionConservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60 degrees when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement.

Project description:ImportanceWhole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown.ObjectiveTo characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors.DesignUnselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic children's hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record.Main outcomes and measuresClinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations.ResultsOf the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%).Conclusions and relevanceTumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors.

Dataset Information

Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

Background

Methods

Results

Conclusion

Publications

Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).

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