UNIPARENTAL DISOMY IN CARTILAGE-HAIR HYPOPLASIA

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder tha t presents with pleiotropic manifestations including impaired skeletal growth and cellular immunity. It is most prevalent among two founder populations, the Old Order Amish in the USA and the Finns. The gene ha s been localized to 9p13 by linkage analysis and linkage disequilibriu m mapping. A statistically significant deficiency of affected members resulting in a lower than expected segregation ratio has been reported in the Amish, but was not found in a previous study in Finnish CHH fa milies. Reduced penetrance was the mechanism suggested in the Amish, b ut could not be verified by haplotype analyses performed after the ass ignment of the CHH gene. Here we have carried out segregation analysis of 101 Finnish CHH families, but again, evidence of a significant def iciency of affected members was not found. Nevertheless, among 54 unip lex families, 2 patients with CHH and uniparental disomy (UPD) for chr omosome 9 were discovered. UPD might contribute to low segregation rat ios by increasing the number of families with only 1 affected individu al. These observations show that UPD may occur in an unexpectedly high number of the patients and should be taken into account in the geneti c counselling and prenatal diagnostics of CHH families.