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.