Groesser, Leopold and Herschberger, Eva and Sagrera, Ana and Shwayder, Tor and Flux, Katharina and Ehmann, Laura and Wollenberg, Andreas and Torrelo, Antonio and Bagazgoitia, Lorea and Diaz-Ley, Blanca and Tinschert, Sigrid and Oschlies, Ilske and Singer, Sebastian and Mickler, Marion and Toll, Agusti and Landthaler, Michael and Real, Francisco X. and Hafner, Christian (2013) Phacomatosis Pigmentokeratotica Is Caused by a Postzygotic HRAS Mutation in a Multipotent Progenitor Cell. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133 (8). pp. 1998-2003. ISSN 0022-202X, 1523-1747
Full text not available from this repository. (Request a copy)Abstract
Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G >C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPIDERMAL NEVUS; MOSAICISM; HAPPLE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 10:31 |
| Last Modified: | 06 Apr 2020 10:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16328 |
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