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Journal of Bone and Mineral Metabolism

, Volume 26, Issue 6, pp 648–652 | Cite as

Grebe-type chondrodysplasia: a novel missense mutation in a conserved cysteine of the growth differentiation factor 5

  • Muhammad Faiyaz-Ul-Haque
  • Eissa A. Faqeih
  • Hamad Al-Zaidan
  • Amal Al-Shammary
  • Syed H. E. Zaidi
Short Communication

Abstract

Grebe-type chondrodysplasia is a congenital skeletal disorder that is characterized by markedly shortened limbs and very short digits. This defect has an autosomal recessive mode of inheritance and results from mutations in the growth differentiation factor 5 (GDF5) gene. Here, we report three affected children in a consanguineous family who display typical features of Grebe-type chondrodysplasia. Sequencing of the GDF5 genes of the affected children identified a novel c.1285T>C mutation encoding a p.Cys429Arg substitution. The Cys429 of human GDF5 belongs to a group of seven cysteines, which are highly conserved across species and among the various members of the transforming factor-beta (TGF-β) super family of proteins. These cysteines are essential for the structure, processing, and activity of these proteins. Therefore, it is possible that the p.Cys429Arg change in the GDF5 has produced an inactive protein, resulting in a Grebe-type chondrodysplasia phenotype in the affected children. The absence of skeletal abnormalities in the carrier parents suggests that the p.Cys429Arg change did not produce a dominant negative effect or haploinsufficiency in these individuals. This finding differs from the previous report of skeletal abnormalities in heterozygous individuals of Grebe-type chondrodysplasia families.

Key words

autosomal recessive CDMP-1 GDF5 Grebe-type chondrodysplasia mutation in conserved cysteine 

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Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Muhammad Faiyaz-Ul-Haque
    • 1
  • Eissa A. Faqeih
    • 2
  • Hamad Al-Zaidan
    • 3
  • Amal Al-Shammary
    • 1
  • Syed H. E. Zaidi
    • 4
  1. 1.Molecular Genetics Laboratory, Department of Pathology & Laboratory MedicineKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  2. 2.Department of Pediatric MedicineChildren’s Hospital, King Fahad Medical CityRiyadhSaudi Arabia
  3. 3.Department of Medical GeneticsKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  4. 4.Department of MedicineUniversity Health Network & University of TorontoTorontoCanada

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