Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis
<p><strong>Introduction</strong> Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored.</...
| Autors principals: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
BMJ Publishing Group
2019
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| _version_ | 1826306647004282880 |
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| author | Sadler, B Haller, G Antunes, L Bledsoe, X Morcuende, J Giampietro, P Raggio, C Miller, N Kidane, Y Wise, CA Amarillo, I Walton, N Seeley, M Johnson, D Jenkins, C Jenkins, T Oetjens, M Tong, RS Druley, TE Dobbs, MB Gurnett, CA |
| author_facet | Sadler, B Haller, G Antunes, L Bledsoe, X Morcuende, J Giampietro, P Raggio, C Miller, N Kidane, Y Wise, CA Amarillo, I Walton, N Seeley, M Johnson, D Jenkins, C Jenkins, T Oetjens, M Tong, RS Druley, TE Dobbs, MB Gurnett, CA |
| author_sort | Sadler, B |
| collection | OXFORD |
| description | <p><strong>Introduction</strong> Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored.</p> <p><strong>Methods</strong> Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs. CNV calls were filtered to include only highly confident CNVs with >10 average reads per region and mean log-ratio of coverage consistent with single-copy duplication or deletion. The frequency of 55 common recurrent CNVs was determined and correlated with clinical characteristics.</p> <p><strong>Results</strong> Distal chromosome 16p11.2 microduplications containing the gene <em>SH2B1</em> were found in 0.7% of AIS cases (8/1197). We replicated this finding in two additional AIS cohorts (8/1097 and 2/433), resulting in 0.7% (18/2727) of all AIS cases harbouring a chromosome 16p11.2 microduplication, compared with 0.06% of local controls (1/1664) and 0.04% of published controls (8/19584) (p=2.28×10<sup>−11</sup>, OR=16.15). Furthermore, examination of electronic health records of 92 455 patients from the Geisinger health system showed scoliosis in 30% (20/66) patients with chromosome 16p11.2 microduplications containing <em>SH2B1</em>compared with 7.6% (10/132) of controls (p=5.6×10<sup>−4</sup>, OR=3.9).</p> <p><strong>Conclusions</strong> Recurrent distal chromosome 16p11.2 duplications explain nearly 1% of AIS. Distal chromosome 16p11.2 duplications may contribute to scoliosis pathogenesis by directly impairing growth or by altering expression of nearby genes, such as <em>TBX6</em>. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.</p> |
| first_indexed | 2024-03-07T06:51:08Z |
| format | Journal article |
| id | oxford-uuid:fc99bd86-f758-497f-8004-e0c9d8f34d87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:51:08Z |
| publishDate | 2019 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:fc99bd86-f758-497f-8004-e0c9d8f34d872022-03-27T13:22:06ZDistal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fc99bd86-f758-497f-8004-e0c9d8f34d87EnglishSymplectic Elements at OxfordBMJ Publishing Group2019Sadler, BHaller, GAntunes, LBledsoe, XMorcuende, JGiampietro, PRaggio, CMiller, NKidane, YWise, CAAmarillo, IWalton, NSeeley, MJohnson, DJenkins, CJenkins, TOetjens, MTong, RSDruley, TEDobbs, MBGurnett, CA<p><strong>Introduction</strong> Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored.</p> <p><strong>Methods</strong> Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs. CNV calls were filtered to include only highly confident CNVs with >10 average reads per region and mean log-ratio of coverage consistent with single-copy duplication or deletion. The frequency of 55 common recurrent CNVs was determined and correlated with clinical characteristics.</p> <p><strong>Results</strong> Distal chromosome 16p11.2 microduplications containing the gene <em>SH2B1</em> were found in 0.7% of AIS cases (8/1197). We replicated this finding in two additional AIS cohorts (8/1097 and 2/433), resulting in 0.7% (18/2727) of all AIS cases harbouring a chromosome 16p11.2 microduplication, compared with 0.06% of local controls (1/1664) and 0.04% of published controls (8/19584) (p=2.28×10<sup>−11</sup>, OR=16.15). Furthermore, examination of electronic health records of 92 455 patients from the Geisinger health system showed scoliosis in 30% (20/66) patients with chromosome 16p11.2 microduplications containing <em>SH2B1</em>compared with 7.6% (10/132) of controls (p=5.6×10<sup>−4</sup>, OR=3.9).</p> <p><strong>Conclusions</strong> Recurrent distal chromosome 16p11.2 duplications explain nearly 1% of AIS. Distal chromosome 16p11.2 duplications may contribute to scoliosis pathogenesis by directly impairing growth or by altering expression of nearby genes, such as <em>TBX6</em>. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.</p> |
| spellingShingle | Sadler, B Haller, G Antunes, L Bledsoe, X Morcuende, J Giampietro, P Raggio, C Miller, N Kidane, Y Wise, CA Amarillo, I Walton, N Seeley, M Johnson, D Jenkins, C Jenkins, T Oetjens, M Tong, RS Druley, TE Dobbs, MB Gurnett, CA Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title | Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title_full | Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title_fullStr | Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title_full_unstemmed | Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title_short | Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis |
| title_sort | distal chromosome 16p11 2 duplications containing sh2b1 in patients with scoliosis |
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