Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation

Renata Bocciardi, Roberto Giorda, Jens Buttgereit, Stefania Gimelli, Maria Teresa Divizia, Silvana Beri, Silvio Garofalo, Sara Tavella, Margherita Lerone, Orsetta Zuffardi, Michael Bader, Roberto Ravazzolo, Giorgio Gimelli

Research output: Contribution to journalArticlepeer-review


Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. We report the molecular characterization of a de novo balanced t(2;7) (q37.1;q21.3) translocation in a young female with Marfanoid habitus and skeletal anomalies. The translocation was characterized by fluorescence in situ hybridization (FISH), checked for other abnormalities by array-comparative genomic hybridization (CGH), and finally, the breakpoints were cloned, sequenced, and compared. Biochemical dosage was applied to study the possible mechanisms that may cause the proposita's phenotype. The breakpoint on chromosome 2 disrupts the hypothetical gene MGC42174 (HUGO-approved symbol DIS3L2) and is located in the proximity of the NPPC gene coding for C-type natriuretic peptide (CNP), a molecule that regulates endochondral bone growth. CNP plasma concentration was doubled in the proband compared to five normal controls, while NPPC was substantially overexpressed in her fibroblasts. A transgenic mouse generated to target NPPC overexpression in bone showed a phenotype highly reminiscent of the patient's phenotype. The breakpoint on chromosome 7 is localized proximally at about 75 kb from the COL1A2 gene. The COL1A2 allele on the derivative chromosome was strongly underexpressed in fibroblasts, but total collagen was not significantly different from controls. Several evidences support the conclusion that the proband's abnormal phenotype is associated with C-type natriuretic peptide overexpression.

Original languageEnglish
Pages (from-to)724-731
Number of pages8
JournalHuman Mutation
Issue number7
Publication statusPublished - Jul 2007


  • Balanced translocation
  • Bone anomalies
  • COL1A2
  • DIS3L2
  • Marfanoid habitus
  • MGC42174
  • NPPC

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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