These two authors contributed equally to this work.
An updated mutation spectrum in an Australian series of PJS patients provides further evidence for only one gene locus
Article first published online: 6 OCT 2006
2006 Blackwell Munksgaard
Volume 70, Issue 5, pages 409–414, November 2006
How to Cite
Chow, E., Meldrum, C., Crooks, R., Macrae, F., Spigelman, A. and Scott, R. (2006), An updated mutation spectrum in an Australian series of PJS patients provides further evidence for only one gene locus. Clinical Genetics, 70: 409–414. doi: 10.1111/j.1399-0004.2006.00704.x
- Issue published online: 6 OCT 2006
- Article first published online: 6 OCT 2006
- Received 29 May 2006, revised and accepted for publication 31 August 2006
- disease characteristics;
- MLPA assay;
- STK11 mutations
The genetic predisposition Peutz–Jeghers Syndrome (PJS) has been shown to be associated with mutations in the serine threonine kinase 11 (STK11) gene but only a proportion of probands have been shown to harbour changes in the gene. The remaining patients were proposed to be either associated with a second PJS gene or they harboured more cryptic mutations within the STK11 gene itself. With the introduction of the multiplex ligation probe amplification (MLPA) assay, large sequence losses or gains can be more readily identified. In this report we have screened 33 PJS patients from unrelated families, employing a combination of denaturing high-performance liquid chromatography, direct DNA sequencing and the MLPA assay to identify deleterious changes in the STK11 gene. The results revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene deletions. No phenotypic differences were identified in patients harbouring large deletions in the STK11 gene compared to patients harbouring missense or nonsense mutations. Mutation analysis in PJS should include techniques such as MLPA to identify large exonic or whole-gene deletions and rearrangements. The high proportion of families with identifiable mutations in the STK11 gene using this range of techniques suggests that most, if not all PJS, is attributable to mutations in the STK11 gene, perhaps including as yet undiscovered changes in promoter or enhancer sequences or other cryptic changes.