Progerin

Progerin is a truncated version of lamin A protein involved in Hutchinson-Gilford progeria syndrome. Progerin is most often generated by a silent point mutation (C1824T) in the lamin A gene, LMNA. This mutation activates a cryptic splice site and gives rise to a form of lamin A with a deletion of 50 amino acids near the C-terminus. Approximately 80% of Hutchinson-Gilford progeria syndrome cases are heterozygous for this silent point mutation within exon 11 of the LMNA gene.

Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell; progerin does not properly integrate into the lamina, which disrupts the scaffold structure and leads to significant disfigurement of the nucleus, characterized by a lobular shape. Researchers have shown that progerin activates genes that regulate stem cell differentiation via the Notch signaling pathway.

Researchers are exploring farnesyltransferase inhibitors as a potential pharmacological therapy against the negative effects of progerin on nuclear morphology.

Progerin, which has been linked to normal aging, is produced in healthy individuals via "sporadic use of the cryptic splice site".