ClinVar

Dessars et al. (2009) identified a somatic gln61-to-lys (Q61K) mutation in the NRAS gene in 14 of 27 congenital melanocytic nevi (137550).

In affected skin samples from 8 of 13 patients with congenital melanocytic nevus syndrome (CMNS; 137550), including 4 with neurocutaneous melanosis (NCMS; 249400), Kinsler et al. (2013) identified a somatic heterozygous c.181C-A transversion in the NRAS gene, resulting in a gln61-to-lys (Q61K) substitution in the guanosine triphosphate-binding domain. The mutation was predicted to result in constitutive activation of NRAS. Neurologic samples from 5 patients from whom tissue was available were positive for a somatic Q61K mutation, and the same mutation was present in both neurologic and skin samples when available. Kinsler et al. (2013) concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as associated nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that the mutation may be lethal in the germline.