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A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip

  • Authors:
    • Lihua Zhao
    • Zaiwei Zhou
    • Sun Wang
    • Qing Jiao
    • Jing Wu
    • Feng Ma
    • Lingyan Fan
    • Mengjie Chen
    • Hao Ying
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, P.R. China, Laboratory of Translational Research, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200071, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1773-1778
    |
    Published online on: March 8, 2017
       https://doi.org/10.3892/etm.2017.4191
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Abstract

Developmental dysplasia of the hip (DDH) is a complex disorder of the hip joint affecting 1‑5‰ of newborns. While genetic influence on DDH has been long known, DDH has not been ascribed to any specific genetic event. The present study reported on variants contributing to DDH susceptibility in a family with four individuals affected across three generations. Whole‑exome sequencing was performed in three affected and two unaffected individuals of a pedigree with DDH. Candidate variants were confirmed by Sanger sequencing and then validated in available family members and 37 sporadic DDH patients. Two novel heterozygous, inframe mutations causing multi‑nucleotide substitution polymorphisms (c.1432_1440delCAGCAGCAG corresponding with p.Gln478_480del and c.1440_1441insCAG corresponding with p.Gln480ins) in exon 11 of chromosome 4 in bone morphogenetic proteins‑2‑inducible kinase (BMP2K) were identified; these were found in members of the pedigree affected by DDH and in the unaffected grandmother of the proband, who was deemed to be the carrier of potential mutations, but not in the unaffected normal control saunt of the proband. These two variants shared the same genomic coordinate but with different types of mutation in BMP2K. BMP2K is known to be associated with bone and cartridge development and heterozygous mutations were found to be present in 4/4 (100%) of the affected family members, 4/15 (26.7%) of the unaffected family members and 0/7 (0%) of the unaffected unrelated family members. Genotyping of 37 unrelated, sporadic DDH patients showed that three cases were positive for the BMP2K c.1432_1440delCAGCAGCAG variants (8.12%). These findings provided strong evidence for the role of BMP2K variants in causing DDH and demonstrated that the combination of pedigree information and next‑generation sequencing is an effective method for identifying pathogenic sites associated with DDH.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao L, Zhou Z, Wang S, Jiao Q, Wu J, Ma F, Fan L, Chen M and Ying H: A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip. Exp Ther Med 13: 1773-1778, 2017.
APA
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F. ... Ying, H. (2017). A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip. Experimental and Therapeutic Medicine, 13, 1773-1778. https://doi.org/10.3892/etm.2017.4191
MLA
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F., Fan, L., Chen, M., Ying, H."A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip". Experimental and Therapeutic Medicine 13.5 (2017): 1773-1778.
Chicago
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F., Fan, L., Chen, M., Ying, H."A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip". Experimental and Therapeutic Medicine 13, no. 5 (2017): 1773-1778. https://doi.org/10.3892/etm.2017.4191
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao L, Zhou Z, Wang S, Jiao Q, Wu J, Ma F, Fan L, Chen M and Ying H: A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip. Exp Ther Med 13: 1773-1778, 2017.
APA
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F. ... Ying, H. (2017). A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip. Experimental and Therapeutic Medicine, 13, 1773-1778. https://doi.org/10.3892/etm.2017.4191
MLA
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F., Fan, L., Chen, M., Ying, H."A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip". Experimental and Therapeutic Medicine 13.5 (2017): 1773-1778.
Chicago
Zhao, L., Zhou, Z., Wang, S., Jiao, Q., Wu, J., Ma, F., Fan, L., Chen, M., Ying, H."A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip". Experimental and Therapeutic Medicine 13, no. 5 (2017): 1773-1778. https://doi.org/10.3892/etm.2017.4191
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