BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, but its etiology is unclear. Multiple genetic mutations have been reported to be associated with AIS.

MATERIAL AND METHODS: We enrolled a cohort of 113 surgically treated AIS patients with available parental subjects from the Peking Union Medical College Hospital. We performed whole-exome sequencing in 10 trio families and whole-genome sequencing in 103 singleton patients. Luciferase assay was used to detect the functional alterations of candidate ESR1 and ESR2 variants.

RESULTS: Using a de novo strategy, a missense variant in ESR1 (c.868A>G) was selected as a candidate gene for AIS. The main Cobb angle of this patient was 41° (T6–T10). Another potential pathogenic variant in ESR2 (c.236T>C) was identified. The main curve of the patient was 45° at T10–L3. The transactivation capacities of the mutated ESR1 and ESR2 protein were both significantly decreased (p=0.026 and 0.014, respectively).

CONCLUSIONS: Potential pathogenic variants in ESR1 and ESR2 were identified in 113 AIS patients, suggesting that genetic mutations in ESR1/2 were associated with the risk of AIS.

Keywords: Estrogen Receptor alpha, Estrogen Receptor beta, Mutation, Missense, Scoliosis, Adolescent, Asians, Beijing, Child, Cohort Studies, Cross-Sectional Studies, DNA Mutational Analysis, Polymorphism, Single Nucleotide, Radiography, Spine, Whole Exome Sequencing