FaCD Online Syndrome Fact Sheet

Last updated: 17 Nov 2011

Name: HRAS mutation somatic mosaicism

Mode of Inheritance: spor

Genes

HRAS, mapped to 11p15.5

Tumor features

renal pyelum cancer
urinary bladder cancer

Non-tumor features

nevi

Comment

De novo germline HRAS mutations, in particular p.G12S, and usually arising in the fathers germline, can cause Costello syndrome, which is a complex of particular congenital anomalies, associated with a range of tumors.

Hafner et al[1] reported a patient without signs of Costello syndrome with a large congenital epidermal nevus, urothelial-cell carcinoma of the bladder detected at age 19 years, and two new tumors, in the renal pelvis and bladder, diagnosed at age 48 and lung metastasis at age 49. An HRAS p.G12S mutation was identified in the tumors, nevus and in some normal tissues, but was shown to be absent in a few other normal tissue samples. The authors conclude that post-zygotic somatic mosaicism for HRAS mutations can cause tumors in the absence of signs of Costello syndrome. Somatic mosaicim for p.G12S in patients with signs of Costello syndrome has been reported in a few cases[2].

References

[1] Hafner C, Toll A, Real F.HRAS Mutation Mosaicism Causing Urothelial Cancer and Epidermal Nevus. N Engl J Med 2011; 365:1940-1942
[2] Sol-Church K, Stabley DL, Demmer LA, Agbulos A, Lin AE, Smoot L, Nicholson L, Gripp KW.Male-to-male transmission of Costello syndrome: G12S HRAS germline mutation inherited from a father with somatic mosaicism.Am J Med Genet A. 2009 Mar;149A(3):315-21.