M. Dasouki and D. Markova contributed equally to the work.
Version of Record online: 15 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 143A, Issue 22, pages 2635–2641, 15 November 2007
How to Cite
Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y. and Chu, M.-L. (2007), Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa. Am. J. Med. Genet., 143A: 2635–2641. doi: 10.1002/ajmg.a.31980
How to cite this article: Dasouki M, Markova D, Garola R, Sasaki T, Charbonneau NL, Sakai LY, Chu M-L. 2007. Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa. Am J Med Genet Part A 143A:2635–2641.
- Issue online: 25 OCT 2007
- Version of Record online: 15 OCT 2007
- Manuscript Accepted: 6 JUN 2007
- Manuscript Received: 29 JAN 2007
- National Institutes of Health. Grant Number: GM55625
- National Marfan Foundation
- aortic aneurysm;
- tortuous vessels;
- cutis laxa
Mutations involving elastic tissue proteins result in a broad spectrum of phenotypes affecting skin, skeleton, ocular and vascular structures, including tortuous blood vessels and cutis laxa. Here we report on a female newborn with apparently long fingers, aortic aneurysm, tortuous pulmonary arteries and mild generalized lax skin. She died at 27 days of age due to severe respiratory distress and inoperable systemic vascular abnormalities. Skin biopsy showed marked paucity and fragmentation of elastic fibers and autopsy revealed occlusion of the pulmonary artery. DNA analysis identified compound heterozygous mutations ((c.835C > T (p.R279C)/c.1070_1073dupCCGC) in fibulin-4, a recently recognized elastic fiber associated protein. Analyses of dermal fibroblasts from the patient indicated that fibulin-4 mRNAs with the 4-bp duplication transcribed from one allele are probably subject to nonsense-mediated decay, whereas synthesis and secretion of the missense R279C fibulin-4 protein from the other allele is severely impaired. Immunostaining demonstrated a total absence of fibulin-4 fibers in the extracellular matrix deposited by the patient's fibroblasts. Our studies provide evidence that deficiency in fibulin-4 leads to a perinatal lethal condition associated with elastic tissue abnormalities. © 2007 Wiley-Liss, Inc.