説明
<jats:p>Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder that causes premature, rapid aging shortly after birth. Recently, <jats:italic>de novo</jats:italic> point mutations in the <jats:italic>Lmna</jats:italic> gene have been found in individuals with HGPS. <jats:italic>Lmna</jats:italic> encodes lamin A and C, the A‐type lamins, which are an important structural component of the nuclear envelope. The most common HGPS mutation is located at codon 608 (G608G). This mutation creates a cryptic splice site within exon 11, which deletes a proteolytic cleavage site within the expressed mutant lamin A. Incomplete processing of prelamin A results in nuclear lamina abnormalities that can be observed in immunofluorescent studies of HGPS cells. Mouse models, such as <jats:italic>Lmna</jats:italic> knockout, <jats:italic>Zmpste24</jats:italic> knockout, and <jats:italic>Lmna</jats:italic> L530P knockin will help the study of progeria. <jats:italic>Lmna</jats:italic> mutations have also recently been found in patients with atypical forms of progeria. The discovery of the HGPS mutations brings the total number of diseases caused by mutant <jats:italic>Lmna</jats:italic> to nine, underscoring the astonishing spectrum of laminopathies. Future research into HGPS could also provide important clues about the general process of aging and aging‐related diseases.</jats:p>
収録刊行物
-
- Clinical Genetics
-
Clinical Genetics 66 (5), 375-381, 2004-10-11
Wiley