Human Molecular Genetics, Vol 5, 1733-1736, Copyright © 1996 by Oxford University Press
RJ Wenstrup, GT Langland, MC Willing, VN D'Souza and WG Cole
Type V collagen is a constituent of type I collagen-rich fibrils in many
connective tissues and is a regulator of fibril diameter. In tissues, type
V collagen is a heterotrimer with the molecular structure: alpha 1(V)2
alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic
polymorphisms at the pro alpha 1(V) gene (COL5A1) locus cosegregated with
the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three
generation family. Affected family members, who had classical features
including joint hyperextensibility, fragile skin, and widened, atrophic
scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of
intron 65, which resulted in removal of exon 65 sequences from processed
mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the
expected result of this mutation is reduced efficiency in incorporating
mutant pro alpha 1(V) chains into type V collagen molecules and reduced
type V collagen synthesis. These studies indicate that heterozygous
mutations in COL5A1 can result in EDS type I. However, linkage studies in
other EDS I families indicate the disorder is heterogeneous; linkage to
both COL5A1 and COL5A2 was excluded in two other families with EDS I while
a fourth family was concordant for linkage to COL5A1 (Z = 2.11; theta =
0.00).
ARTICLES
A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro alpha 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I)
Division of Human Genetics, Cincinnati Children's Hospital, OH 45229, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. J. Wenstrup, J. B. Florer, J. M. Davidson, C. L. Phillips, B. J. Pfeiffer, D. W. Menezes, I. Chervoneva, and D. E. Birk Murine Model of the Ehlers-Danlos Syndrome: col5a1 HAPLOINSUFFICIENCY DISRUPTS COLLAGEN FIBRIL ASSEMBLY AT MULTIPLE STAGES J. Biol. Chem., May 5, 2006; 281(18): 12888 - 12895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Segev, E. Heon, W. G. Cole, R. J. Wenstrup, F. Young, A. R. Slomovic, D. S. Rootman, D. Whitaker-Menezes, I. Chervoneva, and D. E. Birk Structural Abnormalities of the Cornea and Lid Resulting from Collagen V Mutations Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 565 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ge, N.-S. Seo, X. Liang, D. R. Hopkins, M. Hook, and D. S. Greenspan Bone Morphogenetic Protein-1/Tolloid-related Metalloproteinases Process Osteoglycin and Enhance Its Ability to Regulate Collagen Fibrillogenesis J. Biol. Chem., October 1, 2004; 279(40): 41626 - 41633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Gopalakrishnan, W.-M. Wang, and D. S. Greenspan Biosynthetic Processing of the Pro-{alpha}1(V)Pro-{alpha}2(V)Pro-{alpha}3(V) Procollagen Heterotrimer J. Biol. Chem., July 16, 2004; 279(29): 30904 - 30912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Unsold, W. N. Pappano, Y. Imamura, B. M. Steiglitz, and D. S. Greenspan Biosynthetic Processing of the Pro-alpha 1(V)2Pro-alpha 2(V) Collagen Heterotrimer by Bone Morphogenetic Protein-1 and Furin-like Proprotein Convertases J. Biol. Chem., February 8, 2002; 277(7): 5596 - 5602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schalkwijk, M. C. Zweers, P. M. Steijlen, W. B. Dean, G. Taylor, I. M. van Vlijmen, B. van Haren, W. L. Miller, and J. Bristow A Recessive Form of the Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency N. Engl. J. Med., October 18, 2001; 345(16): 1167 - 1175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Brandt, E. Orberk, R. Weber, I. Werner, O. Busse, B. T. Muller, F. Wigger, A. Grau, C. Grond-Ginsbach, and I. Hausser Pathogenesis of cervical artery dissections: Association with connective tissue abnormalities Neurology, July 10, 2001; 57(1): 24 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bick State-of-the-Art Review: Vascular Thrombohemorrhagic Disorders: Hereditary and Acquired Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 178 - 194. [PDF]
|
|
|
|
|
|
Y. Imamura, I. C. Scott, and D. S. Greenspan The Pro-alpha 3(V) Collagen Chain. COMPLETE PRIMARY STRUCTURE, EXPRESSION DOMAINS IN ADULT AND DEVELOPING TISSUES, AND COMPARISON TO THE STRUCTURES AND EXPRESSION DOMAINS OF THE OTHER TYPES V AND XI PROCOLLAGEN CHAINS J. Biol. Chem., March 17, 2000; 275(12): 8749 - 8759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Grond-Ginsbach, R. Weber, J. Haas, E. Orberk, S. Kunz, O. Busse, I. Hausser, T. Brandt, and B. Wildemann Mutations in the COL5A1 Coding Sequence Are Not Common in Patients With Spontaneous Cervical Artery Dissections Stroke, September 1, 1999; 30 (9): e1887 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Imamura, B. M. Steiglitz, and D. S. Greenspan Bone Morphogenetic Protein-1 Processes the NH2-terminal Propeptide, and a Furin-like Proprotein Convertase Processes the COOH-terminal Propeptide of pro-alpha 1(V) Collagen J. Biol. Chem., October 16, 1998; 273(42): 27511 - 27517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fichard, E. Tillet, F. Delacoux, R. Garrone, and F. Ruggiero Human Recombinant alpha 1(V) Collagen Chain. HOMOTRIMERIC ASSEMBLY AND SUBSEQUENT PROCESSING J. Biol. Chem., November 28, 1997; 272(48): 30083 - 30087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bouma, W. A. Cabral, W. G. Cole, and J. C. Marini COL5A1 Exon 14 Splice Acceptor Mutation Causes a Functional Null Allele, Haploinsufficiency of alpha 1(V) and Abnormal Heterotypic Interstitial Fibrils in Ehlers-Danlos Syndrome II J. Biol. Chem., April 13, 2001; 276(16): 13356 - 13364. [Abstract] [Full Text] [PDF]
|
|