How to Cite this Article: Hisama FM, Lessel D, Leistritz D, Friedrich K, McBride KL, Pastore MT, Gottesman GS, Saha B, Martin GM, Kubisch C, Oshima J. 2011. Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A. Am J Med Genet Part A 155: 3002–3006.
Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A†
Article first published online: 7 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 12, pages 3002–3006, December 2011
How to Cite
Hisama, F. M., Lessel, D., Leistritz, D., Friedrich, K., McBride, K. L., Pastore, M. T., Gottesman, G. S., Saha, B., Martin, G. M., Kubisch, C. and Oshima, J. (2011), Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A. Am. J. Med. Genet., 155: 3002–3006. doi: 10.1002/ajmg.a.34336
- Issue published online: 21 NOV 2011
- Article first published online: 7 NOV 2011
- Manuscript Accepted: 7 SEP 2011
- Manuscript Received: 29 JUN 2011
- NIH. Grant Numbers: CA78088, AG033313
- German Research Foundation
- Ellison Medical Foundation
- American Heart Association
- Hutchinson–Gilford progeria syndrome;
- Werner syndrome;
- lamin A;
- progeroid syndrome;
- genetic disorder;
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. © 2011 Wiley Periodicals, Inc.