ABSTRACT
The mode of Scheuermann's disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives). The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies' anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann's disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene) probably indicates posttranscriptional genetic disorders. The study is under way.
Subject(s)
Cell Differentiation/genetics , Chondrocytes/pathology , Growth Plate/growth & development , Scheuermann Disease/genetics , Adult , Aged , Cell Proliferation , Female , Genetic Association Studies , Growth Plate/metabolism , Hedgehog Proteins/genetics , Humans , Male , Middle Aged , Paired Box Transcription Factors/genetics , Scheuermann Disease/pathologyABSTRACT
A pathogenetic mechanism of the idiopathic scoliosis (IS) has been established on the basis of in-depth morphological and biochemical investigations of structural components of the spine in patients with IS (surgical material). We have shown that IS develops on the basis of disturbance of proteoglycans (PG) synthesis and formation in vertebral growth plates. The found keratan sulphate-related fraction is likely a marker of genetic changes in PGs in IS. Long-term our studies demonstrated a major-gene effect in IS. The study has shown that aggrecan gene expression is significantly decreased in cultivated chondroblasts from patients with IS. The presence of keratan sulphate-related fraction and keratan sulphate increase are associated with lumnican increase.
