Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and Genotype Phenotype Correlation

We propose a longitudinal study of the natural history of the collagen-related disorder
osteogenesis imperfecta (OI). The overall objectives are to 1) obtain a comprehensive
assessment of the natural history and progression of the multiple secondary features of
osteogenesis imperfecta, and 2) further the understanding of genotype-phenotype correlation
using biosamples collected from well-characterized affected individuals. This study is in
part a continuation of protocol 97-CH-0064, and thus will continue to follow individuals with
OI enrolled in that protocol, to incorporate biosamples obtained, and to analyze data
collected under that protocol.

The major objectives of protocol 97-CH-0064 have focused on radiographic features including
scoliosis and rib deformities, bone density, intensive rehabilitation, and physical therapy.
New developments in genetics, bone tissue biology, and pathophysiology of OI in the past
decade, along with the increasing life expectancy of affected individuals, highlight a need
for the continuation and expansion of this natural history study to understand the full
phenotypic disease spectrum, and to generate biobanks of tissue samples from
well-characterized study participants for continued research.

This proposed protocol will:

1. Continue to follow study participants, use biosamples, and analyze data gathered under
protocol 97-CH-0064 (which will be closed upon the start of this protocol).

2. Expand to include currently known collagen-related OI types V-XVIII and potential
additional types, in addition to collagen OI types III and IV included under protocol
97-CH-0064.

3. Extend the age criteria for study participants to include individuals of all ages, with
age at study enrollment targeted to those from birth to 12 years. This will allow us to
follow clinical outcomes of young adults who had aged out of prior NICHD OI research
programs.

The major objectives will focus on:

1. Continued comprehensive assessment of radiographic, bone density, audiology, dental,
cardiovascular, pulmonary, and neurologic manifestations, and physical rehabilitation.
The immediate goals from this will encompass a) identifying underlying contributing
factors and comorbidities for scoliosis, b) gaining insight into occurrence and
progression of cardiac valvular abnormalities, and c) elucidating the pathogenesis of
primary lung parenchymal defects in individuals with OI.

2. Additional comprehensive assessment of endocrine and renal systems. The novel evaluation
of metabolism in individuals with OI will allow understanding of obesity prevalence in
this population.

3. Continued genetic and molecular biology investigations of OI.

- INCLUSION CRITERIA:

- Individuals previously enrolled in 97-CH-0064, or other NICHD OI study protocols for
whom childhood data were collected at the NIH.

- Individuals from birth to age 12 years at enrollment with a diagnosis of OI type III -
XVIII and potential additional types.

- Diagnosis of OI determined by identification of:

1. A mutation in one allele of genes causing autosomal dominant OI types
(COL1A1, COL1A2, or IFITM5), OR

2. at least one mutation in genes that are indicative of the autosomal
recessive OI types.

OR

Individuals with a clinical diagnosis of OI, and a mutation in one of the above genes
identified through the screening protocol.

EXCLUSION CRITERIA:

- Individuals with the diagnosis of OI Type I.

- Individuals who cannot travel to the NIH because of their medical condition.

- Individuals who, in the opinion of the Investigator, are unable to comply with the
protocol or have medical conditions that would potentially increase the risk of
participation.



There are no exclusionary criteria related to race or gender for this protocol.