Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism

N Engl J Med. 1994 Feb 24;330(8):529-34. doi: 10.1056/NEJM199402243300803.


Background: Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal recessive disorder that has recently been mapped to chromosome segment 15q11-q13. The frequency of this disorder is greatly increased in patients with Prader-Willi or Angelman syndrome, both of which involve deletions of chromosome 15q. The P protein is a transmembrane polypeptide that may transport small molecules such as tyrosine, the precursor of melanin. The P gene is located in chromosome segment 15q11-q13.

Methods: We studied the tyrosinase and P genes in three patients with type II oculocutaneous albinism, one of whom also had Prader-Willi syndrome, and in one patient with a milder syndrome known as autosomal recessive ocular albinism. Individual exons of these genes were amplified from the DNA of each patient by the polymerase chain reaction and screened for mutations by simultaneous analyses of single-stranded conformation polymorphisms and heteroduplexes and subsequent DNA sequencing.

Results: Mutations of the P gene were identified in all four patients. These included one frame shift, three missense mutations that result in amino acid substitutions, and one mutation that affects RNA splicing. The patient with Prader-Willi syndrome plus albinism had a typical deletion of the paternal chromosome 15, rendering him hemizygous for a maternally inherited mutant allele of the P gene. The child with ocular albinism was heterozygous for two different mutations in the P gene.

Conclusions: Abnormalities of the P gene are associated with a wide range of clinical phenotypes, including type II oculocutaneous albinism, albinism associated with the Prader-Willi syndrome, and at least some cases of autosomal recessive ocular albinism.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albinism / genetics
  • Albinism, Ocular / genetics*
  • Albinism, Oculocutaneous / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Codon
  • Female
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Monophenol Monooxygenase / genetics
  • Mutation*
  • Pedigree
  • Polymorphism, Genetic / genetics
  • Prader-Willi Syndrome / genetics*


  • Carrier Proteins
  • Codon
  • Membrane Proteins
  • Membrane Transport Proteins
  • OCA2 protein, human
  • Monophenol Monooxygenase