Melanocortin 1 receptor gene

Introduction

Melanocytes do two ways to melanin on the skin hair, and the eyes.

• Eumelanin is a dark pigment which protects against the harmful effects of Ultraviolet radiation (UVR) of the sun.
• Pheomelanin is a lighter pigment, which is associated with increased susceptibility to free radicals UVR damage [1,2].

What is melanocortin 1 receiver gene?

The melanocortin receptor 1 (MC1R) encodes the melanocortin-stimulating hormone receptor (also known as melanocytestimulating hormone or MSH), found on the surface of melanocytes.

• MSH link to MC1R promotes adenylate cyclase, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) [1].
• This changes pigment production from pheomelanin to eumelanin.

MC1R is maps for chromosome 16q24.3, which means it is located on the long arm of chromosome 16, at position 24.3 near the telomere (the protective cap at the end of the chromosome that shortens with each replication) [3].

What are the variants of MC1R gene?

The MC1R gene is highly polymorphic in Caucasian populations, with more than 80 variants described in the population [1–5]. While the exact number of people carrying the MC1R Genetic variants are difficult to determine globally, population-based studies have estimated that 1–2% of the population has a variant allele for this gene This number is highly variable according to region and population.

In populations of northern European descent:

• Four variants of the MC1R gene (V60L, V92M, R151C and R160W) occur, with a frequency of 5%
• Five variants of the MC1R gene (D84E, R142H, I155T, R163Q and D294H) occur in 1–5% of the population
• Other alleles occur at a frequency of less than 1% [6].

What are they MC1R-related phenotypes?

A phenotype it refers to the observable characteristics related to a gene; in the case of the MC1R gene a related phenotype is hair color.

Hair color is a autosomal recessive trait expressed by the MC1R gene.

• Most people with pure red color (RHC) are homozygous for two variants MC1R alleles
• The height penetrance genes (ie R151C, R160W, D294H, and D84E) are denoted as 'R' and almost always result in a red hair color when homozygous (RR) [5–7].
• People with reddish blonde or reddish brown hair are heterozygouscarrying only one hypomorphic variant allele (Rr).

Not all MC1R Variants are associated with red hair.

• Denoted "r", the V60L, R163Q, and V92M variants do not produce red hair when combined with highly penetrating alleles, due to slight functional impairment or normal coupling of the cAMP pathway.
• V60L is common in the general population without RHC (15% ≤), including Asian and Caucasian populations with darker skin, and is considered silent mutation [6].

What are the clinical characteristics of MC1R variants?

People who carry a homozygous (RR) or compound (Rr) heterozygous R allele will often have at least one of the following characteristic features:

• A grade of red, brown, or strawberry blonde hair (scalp and beard)
• White skin
• Light eye color
• Freckles
• Sun sensitivity (poor tan and sun response lentigines)
• Family members with similar characteristics.

What are the complications of MC1R variants?

MC1R germ line mutations has been shown to increase the risk of cutaneous melanoma. MC1R phenotypic traits make an individual more susceptible to ultraviolet rays (UV) Damage and melanoma can occur without excessive exposure to UV rays. In patients with MC1R Genetic variants, melanoma occurs more frequently and at an earlier age at onset than in the general population.

Other germline mutations that increase the risk of melanoma include cyclindependent kinase 2A inhibitor (CDKN2A) and cyclin-dependent kinase 4 (CDK4) [5].

The risk of melanoma due to MC1R the mutation is moderate compared to the one that occurs with CDKN2A and CDK4 mutations MC1R variants can modify CDKN2A penetrance, increasing the incidence and decreasing the age at the onset of melanoma by up to 21 years, compared to people with CDK2NA single mutations [8].

Some studies have suggested individuals with at least one MC1R the variant allele had a 5-15 fold increase in susceptibility to murine v-Raf sarcoma viral oncogene homolog B (BRAF) mutant melanomas [9]. This finding needs further investigation, as other studies have not found the same association.

As they are MC1R variants diagnosed?

A thorough genetic pedigree can indicate if there is a MC1R Genetic variant that runs in the family and its inheritance pattern. Genetic testing may indicate whether there is a strong family history of melanoma in individuals with red hair and other phenotypic features.

However, genetic testing for MC1R Variants are most frequently performed for research purposes. The entire coding region is evaluated by bidirectional Sanger sequence analysis.

What can I do if I have a MC1R variant?

People with probability of having MC1R The variants, who have red or blonde hair, light eye color, and freckles, should be aware that they have an increased risk of melanoma, as well as other forms of skin. Cancer.

Safe sun behavior includes wearing sun protective clothing, applying sunscreen at regular intervals when outdoors, and avoiding frequent or severe sunburn.

The people who carry the MC1R Variant genes should be advised to perform a periodic self-examination of the skin from early adult life and to have their skin checked by a trained health professional. Careful with pigmented and non-pigmented skin lesions with the following characteristics:

• The 'ugly duckling' - the injury looks different from his other injuries
• An injury that enlarges or changes color, shape, and structure.
• An injury with 'ABCD' characteristics:
  • Asymmetry
  • Border irregularity
  • Color variation
  • Diameter> 6mm (large size).