Legg Calve Perthes Disease-  The hunt for genetic associations S Hayek; E Ezra; S Wientroub; D Steinberg *;  N Rosenberg *...
Introduction <ul><li>LCPD is a disease of unknown origin and may be attributed to genetic as well as environmental </li></...
Thrombophilia <ul><li>Intravascular thrombosis may be the causative mechanism of LCPD  </li></ul><ul><li>The role of herit...
Gaucher disease <ul><li>Clinical and radiological findings of </li></ul><ul><li>avascular hip necrosis due to LCPD may be ...
Inherited osteonecrosis <ul><li>Inherited osteonecrosis of the femoral head has recently been found to be associated with ...
Methods <ul><li>Genomic DNA of confirmed LCPD patients was analysed for the following : </li></ul><ul><li>Thrombophilic po...
Results <ul><li>119 LCPD patients were studied  </li></ul><ul><li>Male to female ratio was 3.3 to 1 </li></ul><ul><li>Mean...
Thrombophilic markers in LCPD vs controls Patients and controls were not statistically different 0.93 41/276  (14.9%)  18/...
Gaucher mutations in LCPD patients <ul><li>The prevalence of N370S mutation was 2.5%  </li></ul><ul><li>(6/238 alleles)   ...
Familial osteonecrosis mutations <ul><li>All LCPD patients were negative for COLA21 mutations </li></ul>Conclusion <ul><li...
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Legg Calve Perthes Disease- The hunt for genetic associations

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Legg Calve Perthes Disease- The hunt for genetic associations

  1. 1. Legg Calve Perthes Disease- The hunt for genetic associations S Hayek; E Ezra; S Wientroub; D Steinberg *; N Rosenberg *; D Waldman *; G Kenet * Pediatric Orthopedic Department Tel-Aviv Sourasky Medical Center *Pediatric Coagulation Service, National Hemophilia Center, Sheba Medical Center, Tel Hashomer
  2. 2. Introduction <ul><li>LCPD is a disease of unknown origin and may be attributed to genetic as well as environmental </li></ul><ul><li>risk factors </li></ul><ul><li>Our aim was to evaluate the potential role of genetic factors in LCPD patients. </li></ul><ul><li>We studied mutations causing thrombophilia, Gaucher disease and inherited osteonecrosis </li></ul>
  3. 3. Thrombophilia <ul><li>Intravascular thrombosis may be the causative mechanism of LCPD </li></ul><ul><li>The role of heritable thrombophilic risk factors in pathogenesis of LCPD is controversial </li></ul>Glueck CJ. et al Clin Orthop 1997 Gallistl SJ et al Pediatr Orthop 1999 Hayek S et al J Bone Joint Surg 1999 Sirvbent N et al . J Pediatr Orthop B2000 Hresko T. et al J Bone Joint Surg 2002 Elbridge J. et al Pediatrics 2001 Hresko T. et al J Bone Joint Surg 2002
  4. 4. Gaucher disease <ul><li>Clinical and radiological findings of </li></ul><ul><li>avascular hip necrosis due to LCPD may be indistinguishable from Gaucher disease </li></ul><ul><li>We previously studied Gaucher mutations among LCPD patients and found an increase in their prevalence. </li></ul>Horwitz M et al Hum Mut 1998 Kenet G et al . Blood Cells Molec Dis 2003
  5. 5. Inherited osteonecrosis <ul><li>Inherited osteonecrosis of the femoral head has recently been found to be associated with variant mutations of collagen type II. </li></ul>Liu YF, Chen WM, Lin YF et al . Type II collagen gene variants and inherited osteonecrosis of the femoral head . N Engl J Med. 2005 .
  6. 6. Methods <ul><li>Genomic DNA of confirmed LCPD patients was analysed for the following : </li></ul><ul><li>Thrombophilic polymorphisms: </li></ul><ul><li>Factor-V Lieden, 677T-MTHFR and Factor-II G20210A. </li></ul><ul><ul><li>Results were compared with 276 pediatric controls referred for elective surgery. </li></ul></ul><ul><li>Gaucher mutations: </li></ul><ul><li>N370S, G insertion (84GG), L444P, </li></ul><ul><li>Intron 2(IVS2+1G>A) and R496H </li></ul><ul><li>Enzyme assays were performed for </li></ul><ul><li>confirmation of Gaucher disease status . </li></ul><ul><li>Collagen mutations (COL2A1) of 12q13 gene </li></ul>
  7. 7. Results <ul><li>119 LCPD patients were studied </li></ul><ul><li>Male to female ratio was 3.3 to 1 </li></ul><ul><li>Mean age at diagnosis was -6 y </li></ul><ul><li>(range 1y to 14.9y) </li></ul>CATTERALL CLASSIFICATION HERRING CLASSIFICATION
  8. 8. Thrombophilic markers in LCPD vs controls Patients and controls were not statistically different 0.93 41/276 (14.9%) 18/119 (15.1%) MTHFR 677T 0.99 11/276 (4%) 4/119 (3.4%) Factror II G20210A 0.81 13/276 (4.7%) 7/119 (5.9%) Factor V Lieden P value Controls -# (%) LCPD -# (%) Marker
  9. 9. Gaucher mutations in LCPD patients <ul><li>The prevalence of N370S mutation was 2.5% </li></ul><ul><li>(6/238 alleles) </li></ul><ul><ul><li>4 patients were heterozygous and one was homozygous </li></ul></ul><ul><li>No positive cases for the other mutations. </li></ul><ul><li>26/55 patients had a low threshold (< 1.0) for </li></ul><ul><li> -Glucosidase enzyme activity, </li></ul><ul><li>These findings are lower than the Israeli population carriership data </li></ul><ul><li>(5.8% of Ashkenazi Jews) </li></ul><ul><li>The association with LCPD found in a smaller previous study was </li></ul><ul><li>not confirmed </li></ul>Horwitz M et al Hum Mut 1998 ; Kenet G et al Blood Cells Molec Dis 2003
  10. 10. Familial osteonecrosis mutations <ul><li>All LCPD patients were negative for COLA21 mutations </li></ul>Conclusion <ul><li>We found no evidence that LCPD is associated with any of the genetic factors causing thrombophilia, Gaucher disease or familial osteonecrosis </li></ul>
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