The breakpoint identified in a balanced de novo translocation t(7;9)(p14.1;q31.3) disrupts the a-kinase (PRKA) anchor protein 2 gene (AKAP2) on chromosome 9 in a patient with Kallmann syndrome and bone anomalies

Emanuele Panza, Giorgio Gimelli, Mario Passalacqua, Amnon Cohen, Stefania Gimelli, Sabrina Giglio, Cristina Ghezzi, Bianca Sparatore, Babett Heye, Orsetta Zuffardi, Elena Rugarli, Thomas Meitinger, Giovanni Romeo, Roberto Ravazzolo, Marco Seri

Research output: Contribution to journalArticlepeer-review

Abstract

We report the molecular characterization of a patient with Kallmann syndrome and bone anomalies bearing a balanced de novo translocation t(7;9)(p14.1;q31.3) which completely disrupts the A-kinase anchor protein 2 gene (AKAP2) on chromosome 9. In order to investigate the role of AKAP2 in the pathogenesis of the disease, we analyzed the expression of Akap2 in mouse embryos. The expression pattern was consistent with the phenotype observed and mAkap2 was actually found in the olfactory bulb and in the cartilagineous structures of the embryo. Since AKAP2 is supposed to bind and compartmentalize the PKA, we also analyzed the distribution and quantity of PKA in limpho-blastoid cell lines of the patient compared with a control; these experiments did not demonstrate any differences between the cell lines. Furthermore a collection of 98 DNA samples from sporadic Kallmann patients was screened for mutations in this gene. The analysis revealed two different sequence variations observed in two patients but not in 200 control chromosomes: since they have been detected also in the unaffected mother of one of the two patients we can assume that they are rare polymorphisms, although we cannot exclude that they represent mutations with incomplete penetrance. Our findings suggest that the complex phenotype with Kallmann syndrome and bone anomalies observed in our patient could be the result of the interruption of the AKAP2 gene. However, a position effect mediated by the translocation could not be excluded. The screening of AKAP2 in other Kallmann patients will be necessary to elucidate its role in the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalInternational Journal of Molecular Medicine
Volume19
Issue number3
Publication statusPublished - Mar 2007

Keywords

  • AKAP2
  • Anosmia
  • Hypogonadotropic hypogonadism
  • Kallmann syndrome
  • UCC1

ASJC Scopus subject areas

  • Genetics

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