From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis

Pérez-Machado, Gisselle; Berenguer-Pascual, Ester; Bovea-Marco, Miquel; Rubio-Belmar, Pedro Antonio; García-López, Eva; Garzón, María José; Mena-Mollá, Salvador; Pallardó, Federico V.; Hermida, Teresa Bas; Viña, Juan R.; García‐Giménez, José Luis

doi:10.1016/j.bone.2020.115563

Cited by 42 publications

(58 citation statements)

References 129 publications

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“…Additionally, this cohort showed minimal overlap in specific genes across families. Our results support and add to the growing evidence that AIS is a highly polygenic disorder [ 7 , 8 , 28 , 79 , 80 ] in which multiple variants of variable effect size, potentially in combination with epigenetic and environmental phenomenon [ 81 ], contribute to the disease phenotype.…”

Section: Discussionsupporting

confidence: 86%

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease

Terhune

Wethey

Cuevas

et al. 2021

Genes

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Adolescent idiopathic scoliosis (AIS) is a lateral spinal curvature >10° with rotation that affects 2–3% of healthy children across populations. AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown. In this study, we performed exome sequencing of affected individuals within 23 multigenerational families, with the hypothesis that the occurrence of rare, low frequency, disease-causing variants will co-occur in distantly related, affected individuals. Bioinformatic filtering of uncommon, potentially damaging variants shared by all sequenced family members revealed 1448 variants in 1160 genes across the 23 families, with 132 genes shared by two or more families. Ten genes were shared by >4 families, and no genes were shared by all. Gene enrichment analysis showed an enrichment of variants in cytoskeletal and extracellular matrix related processes. These data support a model that AIS is a highly polygenic disease, with few variant-containing genes shared between affected individuals across different family lineages. This work presents a novel resource for further exploration in familial AIS genetic research.

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Section: Discussionsupporting

confidence: 86%

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease

Terhune

Wethey

Cuevas

et al. 2021

Genes

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“…A total of 895 genes associated with scoliosis extracted using HPO were reviewed. An additional 16 genes reported in the literature based on Perez-Machado and colleagues’ 2020 paper since then were also reviewed, of which three were duplicates among the 895 genes already identified, resulting in a total of 908 genes (see Figure 1 ) [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Scoliosis is defined as a coronal plane spine curvature of 10 degrees or greater as measured radiographically and can be separated into idiopathic, congenital, and syndromic or neuromuscular scoliosis. Idiopathic scoliosis represents a curvature of the spine for which no definitive underlying cause is yet known, although a number of candidate genes have been identified [ 11 , 12 ]. Congenital scoliosis is caused by vertebral malformations such as failure of formation (hemivertebrae) and/or failure of segmentation (congenital fusion of two or more vertebral levels).…”

Section: Introductionmentioning

confidence: 99%

A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita

Latypova

Creadore

Dahan‐Oliel

et al. 2021

Genes

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Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.

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“…Radiograph of patient I., 11 years old. Diagnosis: idiopathic uncomplicated progressive compensated scoliosis of the IV degree (50°): a) before the operation, the value of the thoracic scoliotic arch is 50°, b) after the operation, the value of the thoracic scoliotic arch is 0° [15] а а б б окостенения (0-5), где 0 стадия -отсутствие зон оссификации апофизов подвздошных гребней, 5 стадияполное слияние крыльев подвздошных костей с оссифицированными апофизами гребней [16].…”

Section: Figunclassified

“…Таким образом, не только генетическая предрасположенность, но и эпигенетика, обусловленная факторами внешней среды (питание, вирусная нагрузка, лекарства, физической активностью), может способствовать развитию идиопатического сколиоза. Все большее количество доказательств указывает на то, что генетико-экологическое взаимодействие является ключевым элементом, который следует учитывать в этиопатогенезе сколиотической болезни [16]. Генетические исследования последних лет подтверждают, что подростковый идиопатический сколиоз является полигенным заболеванием, возникающим в результате взаимодействия нескольких локусов генов и факторов окружающей среды.…”

Section: идиопатический сколиоз и факторы окружающей средыunclassified

Idiopathic scoliosis: general characteristics and analysis of etiological theories (literature review)

Строкова

Pahomova

Gusev

et al. 2021

Acta biomedica scientifica

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Idiopathic scoliosis is a severe pathology of the musculoskeletal system that affects children and adolescents all over the world. The disease occurs in approximately 0.2-0.6% of the general population, and is the largest subgroup of spinal curvature in humans (70-90% of all known scoliosis cases). In idiopathic scoliosis, a threedimensional deformation of the vertebral column is formed, leading to the formation of a rib hump, curvature of the ribs and chest, asymmetry of the pelvis and impaired development of internal organs. The main feature of the disease is the spontaneous development of deformity during the growth of the child and the tendency to progress. Scoliosis is not only an orthopedic disease, but also a ignificant cosmetic, and, consequently, a psychological and social problem. The standard of treatment for scoliotic disease remains unchanged for a long time: observation, corset treatment and surgical correction. The prognosis for the development of pathology varies depending on the degree of deformation. The corset-therapy, hospitalization, surgery and treatment of chronic back pain have a negative impact on the psychoemotional state of children and adolescents. Despite significant advances in the methods of diagnosis of deformity, improvement of surgical treatment methods and in the study of pathogenesis, the etiological factor of pathology is still unknown. The search for the causes of idiopathic scoliosis covers almost all aspects of its possible origin: genetic, environmental, hormonal, metabolic, biochemical, neurological, and others. In recent decades, relevant theories of the development of scoliosis have been formulated, but none of the theories reveals the essence of the pathological process and has no clear justification. The greatest number of supporters is the genetic theory: genetic factors play a key role in the occurrence and development of idiopathic scoliosis. Understanding the underlying factors of the disease will enable prevention, early diagnosis, and identification of the risk groups of the patients in question.

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From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis

Cited by 42 publications

References 129 publications

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease

A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita

Idiopathic scoliosis: general characteristics and analysis of etiological theories (literature review)

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