Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico

Nat Genet. 2001 Aug;28(4):376-80. doi: 10.1038/ng576.


Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Chromosomes, Human, Pair 3 / genetics*
  • DNA Mutational Analysis
  • Female
  • Founder Effect
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease
  • Genotype
  • Hermanski-Pudlak Syndrome / epidemiology
  • Hermanski-Pudlak Syndrome / genetics*
  • Homozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Molecular Sequence Data
  • Mutation
  • Organ Specificity
  • Pedigree
  • Phenotype
  • Physical Chromosome Mapping
  • Puerto Rico / epidemiology
  • Sequence Deletion


  • Carrier Proteins
  • HPS3 protein, human
  • Intracellular Signaling Peptides and Proteins

Associated data

  • GENBANK/AF375663
  • GENBANK/AY033141