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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.
Source Information
From the Departments of Medical Genetics (S.-T.L., R.L., R.A.S.) and Pediatrics (R.L., R.A.S.), University of Wisconsin, Madison; the Department of Genetics, Case Western Reserve University School of Medicine, Cleveland (R.D.N.); the Department of Pediatrics and Child Health, University of Birmingham, Birmingham Maternity Hospital, Edgbaston, Birmingham, United Kingdom (S.B.); and the Department of Ophthalmology, Hospital for Sick Children, Toronto (M.M.).
Address reprint requests to Dr. Spritz at 317 Laboratory of Genetics, 445 Henry Mall, University of Wisconsin, Madison, WI 53706.
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