Hunt for genetic susceptibility in a complex disease

One of the most frequent spine abnormality in early adulthud is adolescent idiopathic scoliosis. It has great significance, since it represents 80% of all types of scoliosis. It is ten times more frequent in girls, than in boys. The mode of inheritance is contraversial, there were data for autosomal dominant, X-linked dominant, or non-mendelian inheritance. So far no candidate genetic locus for IS has been identified. By comparing the gene expression levels in paraventral muscle between the two sides of the spine in IS patients 11 candidate genes were identified for further investigation. With restriction fragment length polymorphism analysis of these genes a polymorphism in the gene of the Bromodomain PHD finger Transcription Factor (BPTF) has been revealed. A deficiency of the sequence appears more frequently in IS (P=0.6) than in control (P=0.21) cases. The molecular basis of the polymorphism is a 4.5 kb deletion in the last intron of the BPTF gene. The BPTF is the human ortholog of Drosophila Nurf301, which is the largest subunit of a chromatin remodeling NURF complex. Malfunction of BPTF in early ontogenesis, together with intense growth rate during adolescence and other environmental factors could influence the development of IS.