Correlation analysis of clinical features and genotype in dogs with intervertebral disc degeneration

2020 ◽  
Vol 1 ◽  
pp. 128-134
Author(s):  
T. Kuznetsova ◽  
◽  
A. Mikhailova ◽  
A. Markov ◽  
E. Filippova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Chromosome 12 ◽  
Genetic Aspect ◽  
Fibroblast Growth ◽  
Degenerative Diseases ◽  
Similar Phenotype ◽  
Fgfr3 Mutations ◽  
Compression Myelopathy

Most modern pet species have awide breed variability. The genetic aspect plays a signif-icant role in the development of individual pathologies. A retrogen encoding fibroblast growth factor 4 (FGF4), when inserted into the chromosome 18of dogs (CFA18), leads to chondrodysplasia, phenotypically mani-festing itself as shortened limbs in dogs. The incorporation of the FGF4 retrogene into chromosome 12 (CFA12) leads to a similar phenotype, but associated with an increased degeneration of the intervertebral discs. Although many retrogens are considered “silent”pseudogenes, the FGF4 retrogene in cases of chondrodysplasia and chondro-dystrophy is transcriptionally activated and leads to hyperactivation of the fi-broblast growth factor 3 receptor (FGFR3). Mutations are dominant, but links with spinal problems have been identified only for one, where the retro-gene is integrated into chromosome 12. Thus, dogs with the phenotype of short limbs are at risk for degenerative disease of the intervertebral discs, however, the disease recorded among animals is not related to chondrodystrophoids. The genetic predispo-sition of dogs of chondrodystrophoid breeds to degeneration of intervertebral discs is not a pathognomonic criterion for its presence. The study included genetic tests of dogs of different breeds, which were examined for compression myelopathy as a result of degeneration of the intervertebral discs. During testing, the purpose of which was to find correlation, the corresponding pedigree predispositions and clinical mani-festations of degenerative diseases of the intervertebral discs among 20 dogs (14 chondrodystrophoid and 6 non-chondrodystrophoid) wereconfirmed, in 14 cases (i.e. 70%) discogenic compres-sion was revealed during tomography.

Molecular Grading of Urothelial Cell Carcinoma With Fibroblast Growth Factor Receptor 3 and MIB-1 is Superior to Pathologic Grade for the Prediction of Clinical Outcome

2003 ◽  
Vol 21 (10) ◽  
pp. 1912-1921 ◽  
Author(s):  
Bas W.G. van Rhijn ◽  
André N. Vis ◽  
Theo H. van der Kwast ◽  
Wim J. Kirkels ◽  
François Radvanyi ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Urothelial Cell Carcinoma ◽  
Fgfr3 Mutation ◽  
Grade 3 ◽  
Fgfr3 Mutations ◽  
Mib 1

Purpose: Fibroblast growth factor receptor 3 (FGFR3) mutations were recently found at a high frequency in well-differentiated urothelial cell carcinoma (UCC). We investigated the relationship between FGFR3 status and three molecular markers (MIB-1, P53, and P27kip1) associated with worse prognosis and determined the reproducibility of pathologic grade and molecular variables. Patients and Methods: In this multicenter study, we included 286 patients with primary (first diagnosis) UCC. The histologic slides were reviewed. FGFR3 status was examined by polymerase chain reaction–single strand conformation polymorphism and sequencing. Expression levels of MIB-1, P53, and P27kip1 were determined by immunohistochemistry. Mean follow-up was 5.5 years (range, 0.4 to 18.4 years). Results: FGFR3 mutations were detected in 172 (60%) of 286 UCCs. Grade 1 tumors had an FGFR3 mutation in 88% of patient samples and grade 3 tumors in 16% of patient samples. Conversely, aberrant expression patterns of MIB-1, P53, and P27kip1 were seen in 5%, 2%, and 3% of grade 1 tumors and in 85%, 60%, and 56% of grade 3 tumors, respectively. In multivariate analysis with recurrence rate, progression, and disease-specific survival as end points, the combination of FGFR3 and MIB-1 proved independently significant in all three cases. By using these two molecular markers, three molecular grades (mGs) could be identified: mG1 (mutation; normal expression), favorable prognosis; mG2 (two remaining combinations), intermediate prognosis; and mG3 (no mutation; high expression), poor prognosis. The molecular variables were more reproducible than pathologic grade (85% to 100% v 47% to 61%). Conclusion: The FGFR3 mutation represents the favorable molecular pathway of UCC. Molecular grading provides a new, simple, and highly reproducible tool for clinical decision making in UCC patients.

Effects of Basic Fibroblast Growth Factor on Spontaneous Resorption of Herniated Intervertebral Discs

Spine ◽  
1999 ◽  
Vol 24 (10) ◽  
pp. 940-945 ◽  
Author(s):  
Akihito Minamide ◽  
Hiroshi Hashizume ◽  
Munehito Yoshida ◽  
Mamoru Kawakami ◽  
Nobuhiro Hayashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Intervertebral Discs ◽  
Fibroblast Growth

scholarly journals Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype

2019 ◽  
Vol 56 (6) ◽  
pp. 895-902 ◽  
Author(s):  
Brian G. Murphy ◽  
Peter Dickinson ◽  
Denis J. Marcellin-Little ◽  
Kevin Batcher ◽  
Stephen Raverty ◽  
...  
Keyword(s):  
Nova Scotia ◽  
Intervertebral Disc ◽  
Structural Changes ◽  
Intervertebral Discs ◽  
Chromosome 12 ◽  
Fibroblast Growth ◽  
Cartilaginous Tissue ◽  
Neurological Sequelae ◽  
Pathologic Features ◽  
Dog Breed

Chondrodystrophy results in predictable and progressive biochemical and structural changes to the intervertebral disc, resulting in early onset degeneration and dystrophic mineralization of the disc. Accelerated degeneration and mineralization of the intervertebral disc are common in multiple dog breeds and can result in compromised function, herniation, pain, and a variety of neurological sequelae. A mutation responsible for chondrodystrophy in dogs has been identified as an aberrant fibroblast growth factor 4 ( FGF4) retrogene insertion on chromosome 12 (CFA12) and is associated with short stature of the Nova Scotia Duck Tolling Retriever. Segregation of the CFA12 FGF4 retrogene in this dog breed provides an opportunity to examine the effect of retrogene presence on radiographic and histologic appearance of chondrodystrophic disc degeneration within a single breed. Here we found that in the intervertebral discs isolated from 2 dogs with the CFA12 FGF4 genotype, the nucleus pulposus was largely replaced by cartilaginous tissue, and physaliferous notochordal cells were rarely if ever identified. These findings are in contrast to the normal histologic findings in 2 breed-matched dogs lacking the mutation. The findings are consistent with premature chondroid degeneration of the intervertebral disc and suggest that the presence of the CFA12 FGF4 retrogene is sufficient to cause the chondrodystrophic phenotype.

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