Hutchinson-Gilford Progeria Syndrome

Hutchinson-Gilford Progeria Syndrome (HGPS) is a lethal congenital disorder, characterised by premature appearance of accelerated ageing in children. Although HGPS was first descri‐ bed by Jonathan Hutchinson [1] and then by Hastings Gilford [2] more than a century ago, it was not until 2003 that the genetic basis of HGPS was uncovered [3, 4]. Approximately 90% of HGPS patients have an identical mutation in paternal allele of the LMNA gene – a substi‐ tution of cytosine to thymine at nucleotide 1824, c.1824C>T. Although apparently a silent mutation (that is, no change in the amino acid, G608G), it causes aberrant mRNA splicing, which leads to the production of a truncated and partially processed pre-lamin A protein called “progerin” [3, 4]. Accumulation of progerin is thought to underlie the pathophysiolo‐ gy of HGPS. Individuals with HGPS appear to show ageing-related phenotypes at a much faster rate than normal, consequently leaving young children with the appearance and health conditions of an aged individual. The reported incidence of HGPS is 1 in 4 to 8 mil‐ lion newborns and 89 patients are currently known to be alive with HGPS worldwide [5]. The observed male to female ratio of incidence of HGPS is 1.2:1 and there has been no report on ethnic-specific recurrence. HGPS affect diverse body systems including growth, skeleton, body fat, skin, hair, and cardiovascular system. However, patients show no defects in their mental and intellectual abilities [6-8]. Surprisingly, progerin has also been found in normal unaffected individuals and its level increases with age, suggesting a similar genetic mecha‐ nism in progeria as in normal physiological ageing. Thus, numerous animal models have been developed to better understand the mechanism(s) of HGPS and to develop cure for this devastating disease.