Journal article
Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis
Journal of medical genetics, Vol.56(7), pp.427-433
07/01/2019
DOI: 10.1136/jmedgenet-2018-105877
PMCID: PMC6592771
PMID: 30803986
Abstract
Introduction 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. Methods 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. Results Distal chromosome 16p11.2 microduplications containing the gene SH2B1 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=2.28x10(-11), 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 SH2B1 compared with 7.6% (10/132) of controls (p=5.6x10(-4), OR=3.9). Conclusions 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 TBX6. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.
Details
- Title: Subtitle
- Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis
- Creators
- Brooke Sadler - Washington University in St. LouisGabe Haller - Washington University in St. LouisLilian Antunes - Washington University in St. LouisXavier Bledsoe - Washington University in St. LouisJose Morcuende - Roy J. and Lucille A. Carver College of MedicinePhilip Giampietro - St. Christopher's Hospital for ChildrenCathleen Raggio - Hospital for Special SurgeryNancy Miller - University of Colorado DenverYared Kidane - Texas Scottish Rite Hospital for ChildrenCarol A. Wise - Texas Scottish Rite Hospital for ChildrenIna Amarillo - Washington University in St. LouisNephi Walton - Geisinger Health SystemMark Seeley - Geisinger Health SystemDarren Johnson - Geisinger Health SystemConner Jenkins - Geisinger Health SystemTroy Jenkins - Geisinger Health SystemMatthew Oetjens - Geisinger Health SystemR. Spencer Tong - Washington University in St. LouisTodd E. Druley - Washington University in St. LouisMatthew B. Dobbs - Washington University in St. LouisChristina A. Gurnett - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.56(7), pp.427-433
- DOI
- 10.1136/jmedgenet-2018-105877
- PMID
- 30803986
- PMCID
- PMC6592771
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Publisher
- Bmj Publishing Group
- Number of pages
- 7
- Grant note
- UL1 TR002345 / Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences of the National Institutes of Health U54HD087011 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P30CA091842 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) UL1TR002345 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) P01HD084387 / Eunice Kennedy Shriver National Institutes of Child Health and Human Development of the National Institutes of Health 81831 / Marfan Foundation Faculty Grant R01AR067715 / National Institute of Arthritis and Musculoskeletal and Skin Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) NIH/NIAMS P30 AR057235 / Washington University Musculoskeletal Research Center U54 HD087011 / Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health P30AR057235 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
- Language
- English
- Date published
- 07/01/2019
- Academic Unit
- Stead Family Department of Pediatrics; Orthopedics and Rehabilitation
- Record Identifier
- 9984304681702771
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