Whole-genome sequencing reveals novel genes in ossification of the posterior longitudinal ligament of the thoracic spine in the Chinese population.

Liang, Chen; Wang, Peng; Liu, Xiao; Yang, Chenlong; Ma, Yunlong; Yong, Lei; Zhu, Bin; Liu, Xiaoguang et al. · J Orthop Surg Res · 2018

case_series · Level IV

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Abstract

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a complex, multifactorial disease. Although several genes that are linked to cervical OPLL susceptibility have been reported, specific genetic studies regarding thoracic OPLL are lacking. Whole-genome sequencing has been considered as an efficient strategy to search for disease-causing genes. We analysed whole-genome sequences in a cohort of 25 unrelated patients with thoracic OPLL. Bioinformatics analysis and various algorithms were used to predict deleterious variants. Sanger sequencing was used to confirm the variants. Four deleterious mutations in three genes (c.2716C>T (p.Arg906Cys) in collagen type VI α6 (COL6A6); c.1946G>C (p.Gly649Ala) in collagen type IX α1 (COL9A1); and c.301T>C (p.Ser101Pro) and c.171A>G (p.Ile57Met) in toll-like receptor 1 (TLR1)) were successfully identified. All the variants were confirmed by Sanger sequencing. The novel deleterious mutations of the three genes may contribute to the development of thoracic OPLL.

Medical subject headings

Anatomy