A novel sequence variant in COL10A1 causing spondylometaphyseal dysplasia accompanied with coxa valga: A case report

Abstract

Rationale: Spondylometaphyseal dysplasia (SMD) is an extremely rare disorder of irregular development of spine and metaphyses of long tubular bones. Mutations in the collagen type X alpha 1 gene were found to underlie this condition. Previously reported mutations in the N-terminal non-collagenous NC2 domain and C-terminal non-collagenous NC1 domain failed to be identified in some specific patients. Patient concerns: A 23-year-old male was referred to us for fixed, angular thoracolumbar kyphosis with semi-paralysis, numbness, and tremor on his left lower limb. Marked hypoplasia of thoracolumbar vertebra and spinal canal stenosis were observed on radiology. Diagnoses: He was diagnosed with spondylometaphyseal dysplasia (Type A4). Gene sequencing was performed using normalized targeted regions sequencing (TRS). A novel heterozygous missense variant p.Gly139Cys in the triple-helical region. Multiple lines of evidence imply this mutation to be pathogenic. Interventions: Posterior instrumentation and vertebral column resection were given to correct his fixed, angular thoracolumbar kyphosis. Outcomes: The correction was satisfying and the functional outcomes were good. Lessons subsections as per style: The findings corroborated that type X collagen plays a critical role in the formation of the human spine as well as the long bones, and further expanded the range of type X collagenopathy. Surgical procedure could be considered for patients with severe malformation and neurological impairments. Abbreviations: ACMG = American College of Medical Genetics and Genomics, BMD = bone mineral density, MCDS = Schmidtype metaphyseal chondrodysplasia, MR = magnetic resonance, PM = moderate pathogenicity, PP = supporting pathogenicity, PS = strong pathogenicity, SD = standard deviation, SMD = spondylometaphyseal dysplasia, TRS = targeted regions sequencing.