Somatic Mosaicism: AKT1 Mutation in the Proteus Syndrome

Constitutive activation of the AKT1 protein underlies overgrowth and tumor susceptibility in this syndrome.

The clinical presentation of Proteus syndrome (segmental or patchy overgrowth of tissues and predisposition to tumors) and its unusual inheritance patterns, including discordance among monozygotic twins, suggests that mosaicism is involved. Mosaicism occurs when an organism is composed of genetically heterogeneous cells. Female mammals are mosaic in that either the paternal X or the maternal X chromosome is randomly inactivated.

The authors performed exome sequencing on paired samples from patients with Proteus syndrome, comparing DNA from affected tissues and from clinically normal skin in the same individual. Twenty-six of 29 patients were found to have the 49G→A (Glu17Lys) mutation in clinically affected tissues or cell lines in the AKT1 …

Reviewing Author

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology