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Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

  • Genetics
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Abstract

Study Design

A hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within the T-box 6 (TBX6) gene and familial idiopathic scoliosis (FIS).

Objective

To determine whether variants within exons of the TBX6 gene segregate with the FIS phenotype within a sample of families with FIS.

Summary of Background Data

Idiopathic scoliosis is a structural curvature of the spine whose underlying genetic etiology has not been established. Idiopathic scoliosis has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis, which suggests that the 2 diseases might have a shared etiology. The TBX6 gene on chromosome 16p, essential to somite development, has been associated with congenital scoliosis in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of the TBX6 gene.

Methods

Parent-offspring trios from 11 families (13 trios; 42 individuals) with FIS were selected for Sanger sequencing of the TBX6 gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p.

Results

Sequencing analyses of the subset of families resulted in the identification of 5 coding variants. Three of the five variants were novel; the remaining 2 variants had previously been characterized and they account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of the TBX6 variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element.

Conclusions

Although this study did not identify any TBX6 coding variants that segregate with FIS, we identified a variant that is located in a potential TBX6 enhancer element. Therefore, further investigation of the region is needed.

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Authors and Affiliations

  1. Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, CO, 80045, USA

    Erin E. Baschal PhD, Kandice Swindle BS, Cambria I. Wethey BA, Alex Poole MS & Nancy H. Miller MD

  2. Genometrics Section, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Baltimore, MD, 21224, USA

    Cristina M. Justice PhD

  3. Musculoskeletal Research Center, Children’s Hospital Colorado, 13123 East 16th Avenue, Aurora, CO, 80045, USA

    Robin M. Baschal BA & Nancy H. Miller MD

  4. Molecular Biology Facility, Stowers Institute, 1000 E. 50th Street, Kansas City, MO, 64110, USA

    Anoja Perera BS

  5. Department of Cell Biology and Development, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404, Illkirch Cedex, France

    Olivier Pourquié PhD & Olivier Tassy PhD

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  1. Erin E. Baschal PhD
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Correspondence to Nancy H. Miller MD.

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Author disclosures: EEB (none); KS (none); CMJ (none); RMB (none); AP (none); CIW (none); AP (none); OP (none); OT (none); NHM (none).

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Baschal, E.E., Swindle, K., Justice, C.M. et al. Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis. Spine Deform 3, 288–296 (2015). https://doi.org/10.1016/j.jspd.2015.01.005

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  • DOI: https://doi.org/10.1016/j.jspd.2015.01.005

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