Evidence of abnormal stromelysin mRNA expression in suspected carriers of otosclerosis: A possible molecular marker

J. R. McPhee, M. A. Gordon, R. J. Ruben, Thomas R Van De Water

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: 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. Design: Skin biopsy specimens were taken in a single blind from human subjects who had been clinically and surgically identified as having otosclerosis. Setting: Subjects were volunteers from the community, identified through hospital records. All procedures were carried out in a clinical research facility. Patients: 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). Intervention: 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 sex-matched negative controls. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1108-1116
Number of pages9
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume119
Issue number10
StatePublished - Jan 1 1993
Externally publishedYes

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Otosclerosis
Matrix Metalloproteinase 3
Messenger RNA
Bone Remodeling
Metalloproteases
Biopsy
Volunteers
Inborn Genetic Diseases
Hospital Records
Thromboplastin
Autoradiography
Genetic Markers
Connective Tissue
Hearing
Complementary DNA
Outcome Assessment (Health Care)
Skin
Research
prostromelysin

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Evidence of abnormal stromelysin mRNA expression in suspected carriers of otosclerosis : A possible molecular marker. / McPhee, J. R.; Gordon, M. A.; Ruben, R. J.; Van De Water, Thomas R.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 119, No. 10, 01.01.1993, p. 1108-1116.

Research output: Contribution to journalArticle

McPhee, J. R. ; Gordon, M. A. ; Ruben, R. J. ; Van De Water, Thomas R. / Evidence of abnormal stromelysin mRNA expression in suspected carriers of otosclerosis : A possible molecular marker. In: Archives of Otolaryngology - Head and Neck Surgery. 1993 ; Vol. 119, No. 10. pp. 1108-1116.
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abstract = "Objective: 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. Design: Skin biopsy specimens were taken in a single blind from human subjects who had been clinically and surgically identified as having otosclerosis. Setting: Subjects were volunteers from the community, identified through hospital records. All procedures were carried out in a clinical research facility. Patients: 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). Intervention: 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 sex-matched negative controls. Results: 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. Conclusion: 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.",
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