Figure 6.

Schematic of the ZMPSTE24-associated progeroid disease severity spectrum. The results presented here and in other studies support the model that a spectrum of progeroid diseases of increasing severity, ranging from MAD-B to atypical progeria to RD, appears to correlate with an increasing amount of uncleaved prelamin A resulting from a failure of ZMPSTE24 cleavage. It has yet to be established whether metabolic syndrome is also directly connected to defects in prelamin A maturation, hence the question mark. The L438F studied here has been reported to be associated with metabolic syndrome (47), but the second patient allele is not known, and whether this mutation is truly causative of metabolic syndrome remains to be established.