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Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
Legg Calve Perthes Disease- The hunt for genetic associations
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Legg Calve Perthes Disease- The hunt for genetic associations

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  • 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. Introduction
    • LCPD is a disease of unknown origin and may be attributed to genetic as well as environmental
    • risk factors
    • Our aim was to evaluate the potential role of genetic factors in LCPD patients.
    • We studied mutations causing thrombophilia, Gaucher disease and inherited osteonecrosis
  • 3. Thrombophilia
    • Intravascular thrombosis may be the causative mechanism of LCPD
    • The role of heritable thrombophilic risk factors in pathogenesis of LCPD is controversial
    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. Gaucher disease
    • Clinical and radiological findings of
    • avascular hip necrosis due to LCPD may be indistinguishable from Gaucher disease
    • We previously studied Gaucher mutations among LCPD patients and found an increase in their prevalence.
    Horwitz M et al Hum Mut 1998 Kenet G et al . Blood Cells Molec Dis 2003
  • 5. Inherited osteonecrosis
    • Inherited osteonecrosis of the femoral head has recently been found to be associated with variant mutations of collagen type II.
    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. Methods
    • Genomic DNA of confirmed LCPD patients was analysed for the following :
    • Thrombophilic polymorphisms:
    • Factor-V Lieden, 677T-MTHFR and Factor-II G20210A.
      • Results were compared with 276 pediatric controls referred for elective surgery.
    • Gaucher mutations:
    • N370S, G insertion (84GG), L444P,
    • Intron 2(IVS2+1G>A) and R496H
    • Enzyme assays were performed for
    • confirmation of Gaucher disease status .
    • Collagen mutations (COL2A1) of 12q13 gene
  • 7. Results
    • 119 LCPD patients were studied
    • Male to female ratio was 3.3 to 1
    • Mean age at diagnosis was -6 y
    • (range 1y to 14.9y)
    CATTERALL CLASSIFICATION HERRING CLASSIFICATION
  • 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. Gaucher mutations in LCPD patients
    • The prevalence of N370S mutation was 2.5%
    • (6/238 alleles)
      • 4 patients were heterozygous and one was homozygous
    • No positive cases for the other mutations.
    • 26/55 patients had a low threshold (< 1.0) for
    •  -Glucosidase enzyme activity,
    • These findings are lower than the Israeli population carriership data
    • (5.8% of Ashkenazi Jews)
    • The association with LCPD found in a smaller previous study was
    • not confirmed
    Horwitz M et al Hum Mut 1998 ; Kenet G et al Blood Cells Molec Dis 2003
  • 10. Familial osteonecrosis mutations
    • All LCPD patients were negative for COLA21 mutations
    Conclusion
    • We found no evidence that LCPD is associated with any of the genetic factors causing thrombophilia, Gaucher disease or familial osteonecrosis

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