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Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2011 Dec; Vol. 155A (12), pp. 3002-6. Date of Electronic Publication: 2011 Nov 07. - Publication Year :
- 2011
-
Abstract
- Classical Hutchinson-Gilford progeria syndrome (HGPS) is caused by LMNA mutations that generate an alternatively spliced form of lamin A, termed progerin. HGPS patients present in early childhood with atherosclerosis and striking features of accelerated aging. We report on two pedigrees of adult-onset coronary artery disease with progeroid features, who were referred to our International Registry of Werner Syndrome (WS) because of clinical features consistent with the diagnosis. No mutations were identified in the WRN gene that is responsible for WS, among these patients. Instead, we found two novel heterozygous mutations at the junction of exon 10 and intron 11 of the LMNA gene. These mutations resulted in the production of progerin at a level substantially lower than that of HGPS. Our findings indicate that LMNA mutations may result in coronary artery disease presenting in the fourth to sixth decades along with short stature and a progeroid appearance resembling WS. The absence of early-onset cataracts in this setting should suggest the diagnosis of progeroid laminopathy. This study illustrates the evolving genotype-phenotype relationship between the amount of progerin produced and the age of onset among the spectrum of restrictive dermopathy, HGPS, and atypical forms of WS.<br /> (Copyright © 2011 Wiley Periodicals, Inc.)
- Subjects :
- Adolescent
Adult
Base Sequence
Child
Coronary Artery Disease diagnosis
Exons
Facies
Female
Humans
Male
Middle Aged
Mutation
Progeria diagnosis
Werner Syndrome genetics
Young Adult
Alternative Splicing
Coronary Artery Disease etiology
Coronary Artery Disease genetics
Lamin Type A genetics
Nuclear Proteins genetics
Progeria complications
Progeria genetics
Protein Precursors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 155A
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 22065502
- Full Text :
- https://doi.org/10.1002/ajmg.a.34336