MPI für molekulare Genetik / Department of Human Molecular Genetics |
|Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2|
|Authors:||Jakobsen, Linda P.; Ullmann, Reinhard; Christensen, Steen B .; Jensen, Karl Erik; Mølsted, Kirsten; Henriksen, Karen F .; Hansen, Claus; Knudsen, Mary A; Larsen, Lars A.; Tommerup, Niels; Tümer, Zeynep|
|Date of Publication (YYYY-MM-DD):||2007-06-01|
|Title of Journal:||Druckausga|
|Journal Abbrev.:||J. Med. Genet.|
|Issue / Number:||6|
|Copyright:||© 2007 by the BMJ Publishing Group Ltd.|
|Review Status:||not specified|
|Abstract / Description:||Background: The Pierre Robin sequence (PRS), consisting of cleft palate, micrognathia and glossoptosis, can be seen as part of the phenotype in other Mendelian syndromes—for instance, campomelic dysplasia (CD) which is caused by SOX9 mutations—but the aetiology of non-syndromic PRS has not yet been unravelled.
Objective: To gain more insight into the aetiology of PRS by studying patients with PRS using genetic and cytogenetic methods.
Methods: 10 unrelated patients with PRS were investigated by chromosome analyses and bacterial artificial chromosome arrays. A balanced translocation was found in one patient, and the breakpoints were mapped with fluorescence in situ hybridisation and Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations, and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out by quantitative real-time PCR.
Results: An abnormal balanced karyotype 46,XX, t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and 800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9 and KCNJ2 mRNA expression was observed in patients with PRS.
Conclusion: Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.
|Comment of the Author/Creator:||Correspondence to:
Dr L P Jakobsen
Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, Panum Institute 24.4., Blegdamsvej 3, 2200 Copenhagen N, Denmark; email@example.com]
|External Publication Status:||published|
|Communicated by:||Hans-Hilger Ropers|
|Affiliations:||MPI für molekulare Genetik|
|External Affiliations:||1.Department of Plastic and Reconstructive Surgery and Burns Unit, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
2.Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, Panum Institute, Copenhagen, Denmark;
3.Department of Orthopaedic Surgery, Section of Paediatric Orthopaedics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
4.Department of Diagnostic Radiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
5.Copenhagen Cleft Palate Centre, Copenhagen, Denmark.
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