Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by many features reminiscent of marked premature aging. The characteristic features include short stature, prominent eyes, micrognathia, craniofacial disproportion, loss of subcutaneous fat, alopecia, beaked nose, "plucked-bird" appearance, coax valga, pathologic bone fractures, atherosclerosis, and cardiovascular disorders. Other clinical features include abnormal and delayed dentition, thin and high pitched voice, pyriform thorax, and short dystrophic clavicles.

At birth, the appearance of patients with Hutchinson-Gilford progeria syndrome is generally normal, but by the first year of age patients show severe growth retardation, balding and sclerodermatous skin changes. Affected children are usually short and thin with an average height of 100 cm or so and average weight of 12-15 kg or even less. Death usually occurs from 7 to 28 years, with a median age of 13.4 years. Over 80% of deaths are due to heart attacks or congestive heart failure.

Hutchinson-Gilford progeria syndrome is caused by mutation in the lamin A (LMNA) gene. Majority of the HGPS cases are sporadic with de novo mutations in LMNA gene. However, in familial cases, studies have suggested both autosomal dominant and recessive inheritance.

Hutchinson-Gilford progeria syndrome is caused by mutation in the lamin A (LMNA) gene. Lamins are type V intermediate filament proteins and have a short N-terminal "head" domain, an alpha-helical "central rod" domain, and a globular tail domain. Lamins are classified as either A or B type according to their primary sequence, expression pattern, and biochemical properties. B-type lamins are expressed in all cells during development and in adult animals, whereas A-type lamins are expressed in differentiated cells. The LMNA gene encodes three A-type lamins: lamin A (LA), lamin C, and lamin A delta-10. Lamin A contains a C-terminal CAAX box, which undergoes methyl esterification and farnesylation. In the process of LA maturation, the C-terminal 18 residues, which include the modified C-terminal cysteine, are removed in two specific cleavage steps.

The most frequent LMNA mutation in Hutchinson-Gilford progeria syndrome is a nucleotide substitution at position 1824, C-to-T, resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This predicts a deletion of 50 basepairs of prelamin A near the C terminus. Low levels of both the mutant mRNA and the mutant protein, LA delta-50, are expressed in fibroblasts derived from Hutchinson-Gilford progeria syndrome patients. In addition, Hutchinson-Gilford progeria syndrome cell nuclei frequently display irregular shapes.