Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 44 (7), 783-7

Postzygotic HRAS and KRAS Mutations Cause Nevus Sebaceous and Schimmelpenning Syndrome

Affiliations

Postzygotic HRAS and KRAS Mutations Cause Nevus Sebaceous and Schimmelpenning Syndrome

Leopold Groesser et al. Nat Genet.

Abstract

Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.

Similar articles

See all similar articles

Cited by 58 PubMed Central articles

See all "Cited by" articles

References

    1. J Dermatol. 2008 Nov;35(11):704-11 - PubMed
    1. J Am Acad Dermatol. 1987 Apr;16(4):899-906 - PubMed
    1. N Engl J Med. 2011 Nov 17;365(20):1940-2 - PubMed
    1. Nat Genet. 2006 Mar;38(3):331-6 - PubMed
    1. Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20780-5 - PubMed

Publication types

MeSH terms

Substances

Feedback