| Abstract #439, Date 2/16/99, Session M, Podium , 8:45a |
| Null expression of COL1A1 in clinical otosclerosis |
| *M.J. McKenna (Harvard Medical School and Massachusetts Eye and Ear Infirmary); A.G. Kristiansen (Massachusetts Eye and Ear Infirmary) |
Otosclerosis shares a striking similarity of clinical, histopathologic and genetic characteristics with mild osteogenesis imperfecta. A recent study has revealed a significant association between clinical otosclerosis and the COL1A1 gene which is known to harbor mutations which result in osteogenesis imperfecta. It has been demonstrated that the majority of mutations in mild osteogenesis imperfecta (type 1) occur within the COL1A1 gene and result in null expression of the mutant allele. We evaluated COL1A1 allelic expression in patients with clinical otosclerosis to determine whether or not a similar pathologic molecular mechanism was responsible for the development of clinical otosclerosis. Patients with clinical otosclerosis and unaffected controls were genotyped for the presence of a four base-pair insertional polymorphism in the 3 prime untranslated region of the COL1A1 gene. Individuals who were heterozygous for the polymorphism were identified. Skin biopsies were obtained, and dermal fibroblast cultures established. After RNA was isolated from these cells, the expression of both COL1A1 alleles was examined using a reverse transcription polymerase chain reaction technique. All four unaffected controls demonstrated expression of both COL1A1 alleles. Two of nine patients with clinical otosclerosis demonstrated expression of only one COL1A1 allele. These results suggest that some cases of clinical otosclerosis may have a similar underlying genetic mechanism as type 1 osteogenesis imperfecta. This work was supported by grant 5 RO1 DC03401 from the National Institute on Deafness and Other Communication Disorders and by grants from the American Otological Society. |