Hutchinson-Gilford Progeria Syndrome (or HGPS or Progeria) is an extremely rare, autosomal dominant, fatal, premature aging syndrome caused by a mutation in the LMNA gene. This mutation causes the over-production of the farnesylated aberrant protein progerin. A single base mutation in LMNA activating an alternative splice site causes over-production of an abnormal lamin A protein named “progerin.” Lamin A, an inner nuclear membrane protein, broadly influences nuclear structure and function. Progerin lacks the proteolytic cleavage site normally used to remove the farnesylated carboxy terminus from lamin A during posttranslational processing. Persistent farnesylation causes progerin accumulation in the inner nuclear membrane and is, at least partly, responsible for HGPS. Researchers now believe that the accumulation of the defective lamin A protein makes the nucleus unstable. That cellular instability leads to the process of premature aging in children with Progeria.
Disease manifestations include severe failure to thrive, scleroderma-like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis leading to heart failure, and debilitating strokes. Without progerin-specific treatment, death occurs at an average age of 14.5 years, usually from accelerated atherosclerosis.
It is estimated that 1 in 20 million people have Progeria. Sixteen children have been identified in the United States, and it is estimated that there are another 400 in the rest of world. As of May 2018, The Progeria Research Foundation (PRF) has 113 living children in their registry. For more information about the epidemiology of Progeria, please click to open the PDF, PRF by the Numbers.
Provided by The Progeria Research Foundation