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The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways.

ABSTRACT: A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1-3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the whole-exome sequencing performed on 113 individuals in 19 multi-generational families with AIS have been filtered and analyzed via interaction pathways and functional category analysis (Varaft, Bingo and Panther). The subsequent list of 2566 variants has been compared to the variants already described in the literature, with an 18% match rate. The familial analysis in two families reveals mutations in the BICD2 gene, supporting the involvement of the muscular system in AIS etiology. The cellular component analysis revealed significant enrichment in myosin-related and neuronal activity-related categories. All together, these results reinforce the suspected role of the neuronal and muscular systems, highlighting the calmodulin pathway and suggesting a role of DNA-binding activities in AIS physiopathology.

SUBMITTER: Marie-Hardy L

PROVIDER: S-EPMC10671325 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways.

Marie-Hardy Laura L Courtin Thomas T Pascal-Moussellard Hugues H Zakine Serge S Brice Alexis A

Genes 20231117 11

A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1-3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the whole-exome sequencing performed on 113 individuals in 19 multi-generational families with AIS have been filtered and analyzed via interaction pathways and functional category analysis ( ...[more]

PMID: 38003035

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Project description:PurposeBrace treatment for adolescent idiopathic scoliosis (AIS) is usually prescribed for 20-40° curves in patients with growth potential. The aim is to reduce the risk of curve progression during growth and to avoid the curve reaching a surgical threshold. Having as small a curve as possible at skeletal maturity will reduce the risk of curve progression during adult life. While evidence exists for brace treatment in AIS, there is disagreement on how and when to discontinue bracing. The purpose of this review was to investigate what criteria have been reported for initiating brace cessation and published weaning protocols and to look at estimates of the number of patients that may progress > 5 degrees after the end of growth.MethodsThis scoping review summarizes existing knowledge on the best time to stop bracing in AIS patients, how to "wean," and what happens to spinal curves after bracing. Searches were carried out through MEDLINE, EMBASE, and PsycINFO in April 2022. A total of 1936 articles were reduced to 43 by 3 reviewers. Full papers were obtained, and data were extracted.ResultsWeaning was most commonly determined by Risser 4 (girls) and 5 (boys). Other requirements included 2 years post-menarche and no growth in standing/sitting height for 6 months. Skeletal maturity assessed from hand and wrist radiographs, e.g., Sanders' stage; distal radius and ulnar physes, could determine the optimal weaning time to minimize curve progression. Complete discontinuation was the most common option at skeletal maturity; variations on weaning protocols involved gradual reduction of bracing over 6-12 months. Curve progression after weaning is common. The 12 studies reporting early curve progression after brace weaning found a mean Cobb angle progression of 3.8° (n = 1655). From the seven studies reporting early curve progression by > 5 degrees, there were 236/700 (34%) patients. There is limited information on risk factors to predict early curve progression after finishing brace treatment with larger curves, especially those over 40 degrees possibly having more chance of progression.ConclusionCurve progression after bracing cessation is a negative outcome for patients who have tolerated bracing for several years, especially if surgery is required. The literature shows that when to start brace cessation and weaning protocols vary. Approximately 34% of patients progressed by more than 5 degrees at 2-4 years after brace cessation or weaning. Larger curves seem more likely to progress. More research is needed to evaluate the risk factors for curve progression after brace treatment, defining the best time to stop bracing based on the lowest risk of curve progression and whether there is any benefit to weaning.

Project description:IntroductionHealth-related quality of life (HRQoL) outcome questionnaire, Scoliosis Research Society (SRS)-30, had been well received since its establishment in 2003. Literatures from Asia on the use of SRS-30 mainly focused on the translation process and validation process, but not on measuring outcomes, particularly in the Chinese community. We carried out a prospective cohort study to evaluate the HRQoL of Chinese AIS adolescents with severe scoliosis after surgery.MethodsOne hundred and four Chinese AIS patients with severe scoliosis undergoing posterior spinal fusion between 2009 and 2013 were recruited in this study. They completed SRS-30 questions before surgery, before hospital discharge, and at follow-up. Mean scores and percentages of individual scores in different domains, and composite scores in terms of subtotal and total scores were calculated referring to the scoring system. Gender-specific and period-specific descriptive analyses were described. Correlation of mean domain scores at the three time points were explored to look for any time-specific relationship. Linear regression analysis looking for potential risk factors on domain scores at different time points by gender were also carried out.ResultsMean age was 16.28 at surgery, and 83.6% were female. Significant correlations between pre-op scores and scores after surgery were observed in function/activity domain (p=0.05) in males, and pain (p=0.04) and satisfaction with management (p=0.04) domains in females. No gender difference in all 5 domain scores at the 3 time points was found. Pre-op maximum Cobb angle and corrected angle were found to be risk factors on self-image, as well as satisfaction with management, in male and female patients.ConclusionsThis is the first report on the evaluation of the clinical HRQoL outcomes of Chinese AIS patients with severe scoliosis after surgery. Medical professionals should pay attention to take care of the difference in personal perceptions of feelings between boys and girls. Special care should also be allocated to AIS patients, and try to arrange earlier surgical intervention.

Project description:The measurements of spinal curvatures using the ultrasound (US) imaging method on children with scoliosis have been comparable with radiography. However, factors influencing the reliability and accuracy of US measurement have not been studied. The purpose of this study is to investigate the effects of curve features and patients' demographics on US measurements and to determine which factors influence the reliability and accuracy. Two hundred children with scoliosis were recruited and scanned with US by one experienced operator and three trainees. One experienced rater measured the proxy Cobb angles from US images twice one week apart and compared the results with clinical radiographic records. The correlation and accuracy between the US and radiographic measurements were subdivided by different curve severities, curve types, subjects' weight status and US acquisition experiences. A total of 326 and 313 curves were recognized from radiographs and US images, respectively. The mean Cobb angles of the 13 missing curves were 17.4±7.4° and 11 at the thoracic region. Among the 16 curves showing large discrepancy (≥6°) between US and radiographic measurements, 7 were main thoracic and 6 were lumbar curves. Twelve had axial vertebral rotation (AVR) greater than 8°. The US scans performed by the experienced operator showed fewer large discrepancy curves, smaller difference and higher correlation than the scans from the trainees (3%, 1.7±1.5°, 0.95 vs 6%, 2.4±1.8°, 0.90). Only 4% missing and 5% large discrepancy curves were demonstrated for US measurements in comparison to radiography. The missing curves were mainly caused by small severity and in the upper spinal region. There was a higher chance of the large discrepancy curves in the main thoracic and lumbar regions with AVR>8°. A skilled operator acquired better US images and led to more accurate measurements especially for those subjects with larger curvatures, AVR and body mass index (BMI).

Dataset Information

The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways.

Publications

The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways.

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