There is strong evidence that otosclerosis is a genetic disease affecting bone remodeling. We propose that, if otosclerosis is genetic, it will manifest itself universally, particularly at the mRNA transcription level.
Skin biopsy specimens were taken in a single blind from human subjects who had been clinically and surgically identified as having otosclerosis.
Subjects were volunteers from the community, identified through hospital records. All procedures were carried out in a clinical research facility.
Twenty-one volunteers underwent a biopsy, including those positively identified as having otosclerosis (n=4), their blood relatives (n=8), or nonrelatives with normal hearing and no known history of otosclerosis (n=9).
Three connective tissue remodeling factors, procollagenase, prostromelysin, and tissue inhibitor of metalloprotease, were analyzed. The mRNA was extracted from each biopsy specimen, hybridized against radiolabeled cDNA, and quantitatively measured by radioautography.
Main Outcome Measure:
We expected to see significant differences in the pattern of mRNA expression for one or more of the three measured bone remodeling factors in otosclerotics, compared with age- and sexmatched negative controls.
Two of the otosclerotic subjects had abnormally low levels of mRNA for prostromelysin and two had higher than normal levels. In three (75%) of the four, variability of mRNA expression among procollagenase, prostromelysin, and metalloprotease tissue inhibitor was higher than normal. Three (38%) of the eight relatives showed a similar pattern and two (22%) of the nine control subjects also tested as abnormal.
This observed variability in otosclerotic subjects might be a manifestation of a genetic control defect, and abnormal stromelysin mRNA expression could serve as a genetic marker for otosclerosis.(Arch Otolaryngol Head Neck Surg. 1993;119:1108-1116)
McPhee JR, Gordon MA, Ruben RJ, Van De Water TR. Evidence of Abnormal Stromelysin mRNA Expression in Suspected Carriers of Otosclerosis: A Possible Molecular Marker. Arch Otolaryngol Head Neck Surg. 1993;119(10):1108–1116. doi:10.1001/archotol.1993.01880220052008
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