Figure 6.

A–D, Assessment of RMRP expression and endonucleolytic cleavage for ribosomal assembly in native cells of one patient from family 2 (P) with anauxetic dysplasia and compound heterozygosity for the RMRP mutations +90_91AG→GC and +14G→A. E and F, Rescue of phenotype by wild-type hyperexpression. A, Expression of RMRP was decreased 13-fold in the patient's lymphocytes and threefold in his fibroblasts (B), compared with average levels in 11 healthy control individuals with (C) and without outliers (C′). Decreased endonucleolytic cleavage in the patient, demonstrated by the increased ratio of 5.8S rRNA bound to ITS-1 versus cleaved 5.8S rRNA of 1.44-fold in lymphocytes (C) and 1.8-fold in fibroblasts (D). E, Rescue of phenotype by wild-type hyperexpression, as shown by the dramatically increasing cell count up to 48 h after transfection (dark bars) in comparison to transfection with the empty vector (pale bars). F, Increase of cell count correlates with increasing endonucleolytic cleavage in ribosomal assembly as measured by the ratio of 5.8S rRNA bound to ITS-1 versus cleaved 5.8S rRNA.