Segregation analysis of idiopathic scoliosis: Demonstration of a major gene effect

Segregation analysis using a model with age and gender effects was applied to 101 pedigrees ascertained through a proband with idiopathic scoliosis, T he transmission probability model was used to detect major gene effect. Whe n we analyzed the pedigrees where affected status was assigned to persons w ith a Cobb's angle of more than 5 degrees we did not detect a significant m ajor gene effect, However, when the affected status was assigned to persons with pronounced forms of disease only (a curve of at least 11 degrees) a s ignificant contribution of a major causal gene could be established and inh eritance could be described according to a dominant major gene diallele mod el, assuming incomplete sex and age dependent penetrance of genotypes, Acco rding to this model, the pronounced forms of idiopathic scoliosis should ne ver occur in the absence of the mutant allele. This indicates that only the carriers of the mutant allele develop pronounced forms of the disease, At the same time, only a fraction of the carriers of the mutant gene should ma nifest the disease (30% of males and 50% of females), Am. J, Med. Genet. 86 :389-394, 1999, (C) 1999 Wiley-Liss, Inc.