Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<jats:sec><jats:title>Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 &gt;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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Distal chromosome 16p11.2 microduplications containing the gene <jats:italic>SH2B1</jats:italic> 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<jats:sup>−11</jats: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 <jats:italic>SH2B1</jats:italic> compared with 7.6% (10/132) of controls (p=5.6×10<jats:sup>−4</jats:sup>, OR=3.9).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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 <jats:italic>TBX6</jats:italic>. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.</jats:p></jats:sec>

Original publication

DOI

10.1136/jmedgenet-2018-105877

Type

Journal article

Journal

Journal of Medical Genetics

Publisher

BMJ

Publication Date

07/2019

Volume

56

Pages

427 - 433