Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11 |
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| Authors: | KA Schrader TN Nelson A De Luca DG Huntsman BC McGillivray |
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| Affiliation: | Department of Medical Genetics, University of British Columbia;, Centre for Translational and Applied Genomics, British Columbia Cancer Agency;, and Department of Pathology and Laboratory Medicine, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada;, and IRCCS CSS-Mendel Institute, Rome, Italy |
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| Abstract: | We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation. |
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| Keywords: | lentiginosis profusa LEOPARD syndrome multiple granular cell tumors multiple lentigines syndrome Schwann cell |
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