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

Veronica A Kinsler, Sayeda Abu-Amero, Peter Budd, Ian J Jackson, Susan M Ring, Kate Northstone, David J Atherton, Neil W Bulstrode, Philip Stanier, Raoul C Hennekam, Neil J Sebire, Gudrun E Moore, Eugene Healy

Research output: Contribution to journalArticle (Academic Journal)

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2026-32
Number of pages7
JournalJournal of Investigative Dermatology
Volume132
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Adolescent
  • Adult
  • Alleles
  • Birth Weight
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Developmental
  • Genotype
  • Germ-Line Mutation
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Nevus, Pigmented
  • Phenotype
  • Prevalence
  • Receptor, Melanocortin, Type 1

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