RMRP mutations in cartilage-hair hypoplasia

Cartilage hair hypoplasia (CHH) or McKusick type metaphyseal chondrodysplasia (MCD) (OMIM # 250250) is due to either the homozygous or compound heterozygous mutations in the nuclear encoded, non-coding RNA gene RMRP. Twenty-seven CHH patients were referred for molecular evaluation of the clinical diagnosis. RMRP mutations were found in 22 patients. The phenotype in one of the five mutation-negative patients was fully congruent with the adopted case definition of CHH. In a second of these patients, the diagnosis of Schmid type MCD (OMIM # 156500) was made and confirmed by the detection of a mutation in the COL10A1 gene. The remaining patients most likely represent one or more MCDs hitherto not yet delineated. The pattern of cumulative growth in infancy and early childhood in the latter four patients was the single feature with greatest negative predictive power for CHH. Fourteen mutations detected here, had not been reported previously. In this ethnically heterogeneous population, we performed a retrospective study to compare the prevalence of clinical features compared to previous reports based mostly on more ethnically homogenous groups.