Figure 1.

Phenotype and identified mutations. (A) Post mortem appearance of fetus A at 16 + 3 weeks pregnancy. Note the edema, extreme micromelia of all four limbs and roentgenographic moth-eaten appearance of tubular bones. The thorax is deformed and narrow. Note the large head with hygroma and the hexadactyly on hands and feet. Scale bar 1 cm. (B) Schematic view of the lamin B receptor as a protein of the inner nuclear membrane and identified mutations. The nucleoplasmatic part interacts directly and indirectly with lamins, chromatin and other nuclear proteins. The transmembrane domain belongs to the C14 sterol reductase family and displays sterol reductase activity. The missense mutations p.N547D and p.R583Q reside in the transmembrane domain (sterol reductase domain). The two frameshift mutations are predicted to create a premature stop codon and thus the RNA is likely to undergo nonsense mediated decay, abolishing both the structural and metabolic function. Missense mutation p.N547D was previously described.²⁸