# PATHOLOGY OF INBORN SKELETAL DISEASES

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1989 · $181,966

## Abstract

Underlying structural defects of collagen are being sought in human
connective tissues diseases.  Of particular interest are those inborn
disorders that affect the musculoskeleton, the more common ones being the
Ehlers-Danlos syndromes, osteogenesis imperfecta, and Marfan's syndrome.  A
rich source of such rare tissues is available to us here and through
collaborative contacts.  Our primary approach is direct analysis of tissue
matrix collagens by biochemical techniques.  A portion of effort is spent
screening promising new cases, but the main effort is devoted to follow-up
studies in depth on identified collagen mutants.  Though collagen disorders
are the prime target, signs of proteoglycan defects would be pursued.  A
major goal is to gain unique insights on the relationship between structure
and function of collagen, as well as helping detect, treat and prevent
these skeletal disorders.  Collagen cross-linking receives keen attention
since cross-linking defects are common to many of the known diseases of the
collagen molecule, and seems a good index of structural integrity.
Techniques include slabgel electrophoresis and reverse phase HPLC
chromatography of collagen polypeptides and derived fragments, and
electronmicroscopy of collagen fibrils and cells in affected tissues.
Where appropriate skin fibroblasts will be grown to characterize
procollagen products.  Appropriate tissue specimens will be frozen for
future DNA and RNA analyses by collaborators should defects be indicated at
the protein level.

Specific cases for follow-up identified in the last two years by tissue
screening include:  1) a new case of EDS VII in which a short deletion
spanning the Alpha2(I)-chain amino-telopeptide domain is indicated; 2) a
new case of EDS VI with no hydroxylysine in skin and lysyl pyridinoline
replacing hydroxylysyl pyridinoline cross-links in cartilage; 3) two lethal
newborn cases of spondylepiphyseal dysplasia in which a structural mutation
of Alpha1(II) is present; 4) achondrogenesis type II (Langer-Saldino) that
totally lacks type II collagen in cartilage; and 5) bone from several cases
of osteogenesis imperfecta.  In addition we will screen for cross-linking
abnormalities in aortic collagen of Marfan's patients.

Inborn disorders that impair the structure and development of the skeleton
account for a significant fraction of the 12 million Americans who have
birth defects.  Collagen abnormalities will account for a significant
number of these.

## Key facts

- **NIH application ID:** 3158030
- **Project number:** 2R01AR037318-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** David R Eyre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $181,966
- **Award type:** 2
- **Project period:** 1986-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158030

## Citation

> US National Institutes of Health, RePORTER application 3158030, PATHOLOGY OF INBORN SKELETAL DISEASES (2R01AR037318-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158030. Licensed CC0.

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