Albinism: Genetics

Abstract

Albinism is a reduction of pigment production in the skin, hair and eyes, plus a variable but characteristic change in eye development. Pigmentation research has shown that albinism is a complex genetic disorder, involving many genes with an array of functions, producing a wide phenotypic spectrum amongst affected individuals. There are currently 24 genetic disorders that have albinism included with the phenotype, including as many as 7 nonsyndromic forms of oculocutaneous albinism (reduced pigment affects skin, hair and eyes), 1 nonsyndromic form of ocular albinism (reduced pigment affects eyes only) and 16 syndromic disorders. The gene functions of the nonsyndromic forms are thought to be involved in melanin biosynthesis and many of the genes associated with the syndromic forms are involved in protein trafficking and vesicular function. Common genetic variants within some of these genes are also associated with normal variation in eye, hair and skin colouration.

Key Concepts

  • All animals make melanin as the chief form of colouration.
  • Melanin is made in specific cells called melanocytes.
  • Albinism is caused by a reduction or absence of melanin biosynthesis resulting in several clinical features.
  • There are many different types of albinism.
  • There are several genes associated with albinism.
  • The molecular pathology of albinism is complex and involves different pathways and different types of mutations.
  • Variation in skin pigmentation involves common polymorphisms in some albinism related genes.
  • Albinism can affect interactions between individuals and society.

Keywords: oculocutaneous albinism; tyrosinase; nystagmus; melanin; pigmentation

Figure 1. Melanin pathway. The initial substrate for melanin biosynthesis is the amino acid tyrosine. The rate‐limiting enzyme is tyrosinase (TYR), which has both tyrosine hydroxylase and dopa oxidase activity. In the presence of sulfhydral‐containing compounds, such as cysteine, pheomelanin is produced through the compound cysteinyldopa. In the absence of sulfhydral groups, black‐brown eumelanin is synthesized. Two other enzymes are involved in the eumelanin pathway, dopachrome tautomerase (TYRP2), and dihydroxyindolecarboxylic acid (DHICA) oxidase (TYRP1).
Figure 2. Structure of tyrosinase. Tyrosinase is a copper‐containing enzyme and the rate‐limiting enzyme in melanin biosynthesis. This figure shows the coding region of the TYR gene (529 amino acids). The signal peptide is important in protein trafficking and translation on membrane‐bound ribosomes. The boxes shown as CuA and CuB are the two copper binding regions. The circles show the location of cysteine residues and the EGF is an epidermal growth factor‐like region. Arrows indicate the location of possible glycosylation sites. There is also a dileucine motif in the 3¢ end of the enzyme that is important in intracellular trafficking of the enzyme to the melanosome.
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Web Links

The Albinism Database, www.ifpcs.org/albinism/ (accessed 9 September 2018).

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Oetting, William S, and Adams, David(Nov 2018) Albinism: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006081.pub3]