Germline melanocortin-1-receptor genotype is associated with severity of cutaneous phenotype in congenital melanocytic nevi: a role for MC1R in human fetal development

Kinsler, Veronica A., Abu-Amero, Sayeda, Budd, Peter, Jackson, Ian J., Ring, Susan M., Northstone, Kate, Atherton, David J., Bulstrode, Neil W., Stanier, Philip, Hennekam, Raoul C., Sebire, Neil J., Moore, Gudrun E. and Healy, Eugene (2012) Germline melanocortin-1-receptor genotype is associated with severity of cutaneous phenotype in congenital melanocytic nevi: a role for MC1R in human fetal development. Journal of Investigative Dermatology, 132, 2026-2032. (doi:10.1038/jid.2012.95). (PMID:22572819)

Abstract

Congenital melanocytic nevi (CMN) are pigmented birthmarks that affect up to 80% of the skin surface area. The increased frequency of CMN in families of severely affected individuals is suggestive of a predisposing germline genotype. We noted a high prevalence of red hair in affected families, and considered a role for MC1R in this condition. A cohort of 166 CMN subjects underwent pigmentary phenotyping, with MC1R genotyping in 113. Results were compared with a local control group of 60 unrelated children and with 300 UK children without CMN. CMN subjects had higher prevalences of red hair and a red-haired parent than local controls and had a higher rate of compound heterozygosity and homozygosity for MC1R variants. The presence of a V92M or R allele (D84E, R151C, R160W, D294H) was associated with increasing size of the CMN, implying a growth-promoting effect of these alleles. Unexpectedly, the V92M and R151C alleles were also strongly associated with birth weight in the CMN cohort, a finding confirmed in the control group. The effect of germline MC1R genotype on development and severity of CMN led us to investigate potential broader effects on growth, revealing a role for MC1R in normal fetal development.Journal of Investigative Dermatology advance online publication, 10 May 2012; doi:10.1038/jid.2012.95.

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