Progeria

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Progeria is usually Werner Syndrome (WS, human progeroid disorder) which is a very rare genetic disease which resembles premature aging. It is most common in those of Japanese ancestory. Another phenotype called Hutchinson-Gilford progeria syndrome also exists with premature, rapid aging shortly after birth. Skin changes are the earliest distinctive clinical finding. Both this and restrictive dermopathy are characterised by misshapen cell nuclei.

Contents

Characteristics

Werner syndrome

Early onset of:

Hutchinson-Gilford syndrome

Very early onset skin changes, perhaps in utero. Death by 10 years. Also as well as above has[1]:

Aetiology

Werner syndrome

Mutations in the WRN gene (encodes for a RecQ helicase) lead to chromosome breaks and translocations, with at the molecular level multiple, large DNA deletions. Helicases unwind double helix RNA and DNA for transcription/replication. Collegen synthesis appears to be specifically changed. Specific impairment of human telomere replcation and stability.

Hutchinson-Gilford syndrome

Mutations in the LMNA gene at 1q21.2 coding for lamin A and lamin C. There are defects in processing of prelamin A through alterations in farnesylation. The common HGPS mutation is located at codon 608 (G608G) which deletes a proteolytic cleavage site within lamin A and prevents prolamin processing. This results in nuclear lamina abnormalities. There is a variant with myopathy.

Restrictive dermopathy

Caused by mutations of the ZMPSTE24 gene at 1p34 causing loss of function of the zinc metalprotylase prelamin A-processing enzyme. This prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A.

Importance

This is used as a model of ageing, but it is only a partial model. Polymorphisms in the WRN gene do not influence the aging-trajectories and survival in the population at large. Ref. Kuningas M, Slagboom PE, Westendorp RG, van Heemst D. Impact of genetic variations in the WRN gene on age related pathologies and mortality. Mech Ageing Dev. 2006 Jan 4.

History

Otto Werner described Werner syndrome in 1904.