Human Molecular Genetics, Vol 7, 249-255, Copyright © 1998 by Oxford University Press
K Michalickova, M Susic, MC Willing, RJ Wenstrup and WG Cole
Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder
that severely impairs the structure and function of the skin, joints, eyes
and blood vessels. We have identified mutations of the COL5A2 gene, which
encodes the alpha2(V) chain of type V collagen, in two unrelated patients
with the severe type I form of EDS. The first proband was heterozygous for
a 7 bp deletion that resulted in skipping of exon 27 while the second
proband was heterozygous for a single nucleotide substitution that resulted
in skipping of exon 28. Cultured dermal fibroblasts from both probands
produced about equal amounts of the normal and mutant alpha2(V) mRNAs and
protein chains. The dermis from the first proband contained a sparse
collagen fibrillar network with great variability in collagen fibril sizes
and shapes. The dermal collagens were also abnormally soluble. Bone cells
from the first proband also produced about equal amounts of the normal and
mutant alpha2(V) mRNAs. However, the collagen fibrillar architecture and
collagen solubility of the bone matrix were normal. Our findings show that
heterozygous mutations of the COL5A2 gene can produce the EDS type I
phenotype. They also suggest that type V collagen plays a more important
role in collagen fibrillogenesis of dermis than that of bone.
ARTICLES
Mutations of the alpha2(V) chain of type V collagen impair matrix assembly and produce ehlers-danlos syndrome type I
Division of Orthopaedics, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
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