Journal of Bone and Mineral Metabolism

, Volume 25, Issue 3, pp 159–164 | Cite as

Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation

  • Elahe Elahi
  • Yousef Shafaghati
  • Sareh Asadi
  • Farnaz Absalan
  • Hani Goodarzi
  • Nava Gharaii
  • Mohammad Hassan Karimi-Nejad
  • Farhad Shahram
  • Anne E. Hughes
ORIGINAL ARTICLE

Abstract

Familial expansile osteolysis (FEO) is a rare disorder causing bone dysplasia. The clinical features of FEO include early-onset hearing loss, tooth destruction, and progressive lytic expansion within limb bones causing pain, fracture, and deformity. An 18-bp duplication in the first exon of the TNFRSF11A gene encoding RANK has been previously identified in four FEO pedigrees. Despite having the identical mutation, phenotypic variations among affected individuals of the same and different pedigrees were noted. Another 18-bp duplication, one base proximal to the duplication previously reported, was subsequently found in two unrelated FEO patients. Finally, mutations overlapping with the mutations found in the FEO pedigrees have been found in ESH and early-onset PDB pedigrees. An Iranian FEO pedigree that contains six affected individuals dispersed in three generations has previously been introduced; here, the clinical features of the proband are reported in greater detail, and the genetic defect of the pedigree is presented. Direct sequencing of the entire coding region and upstream and downstream noncoding regions of TNFRSF11A in her DNA revealed the same 18-bp duplication mutation as previously found in the four FEO pedigrees. Additionally, eight sequence variations as compared to the TNFRSF11A reference sequence were identified, and a haplotype linked to the mutation based on these variations was defined. Although the mutation in the Iranian and four of the previously described FEO pedigrees was the same, haplotypes based on the intragenic SNPs suggest that the mutations do not share a common descent.

Key words

familial expansile osteolysis TNFRSF11A RANK haplotype DNA repeat sequences 

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Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Elahe Elahi
    • 1
    • 2
    • 3
  • Yousef Shafaghati
    • 4
  • Sareh Asadi
    • 1
  • Farnaz Absalan
    • 1
    • 2
  • Hani Goodarzi
    • 5
  • Nava Gharaii
    • 5
  • Mohammad Hassan Karimi-Nejad
    • 6
  • Farhad Shahram
    • 7
  • Anne E. Hughes
    • 8
  1. 1.National Institute for Genetic Engineering and BiotechnologyTehran-Karaj ExpresswayTehranIran
  2. 2.Dept. of Biological Sciences, Faculty of ScienceUniversity of TehranTehranIran
  3. 3.Bioinformatics Center, Institute of Biochemistry and BiophysicsUniversity of TehranTehranIran
  4. 4.Genetics Research CenterUniversity of Welfare Science and Rehabilitation at EvinTehranIran
  5. 5.Dept. of Biotechnology, Faculty of ScienceUniversity of TehranTehranIran
  6. 6.Karimi-Nejad/Najmabadi Genetics CenterTehranIran
  7. 7.Rheumatology Research CenterTehran University of Medical SciencesTehranIran
  8. 8.Dept. of Medical GeneticsThe Queen's University of BelfastBelfastUK

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