RCMI International Symposium on Health Disparities
November 12-15, 2000
San Juan, Puerto Rico

Invited Speakers

GENETICS OF HERMANSKI-PUDLAK SYNDROME -
AN UNUSUAL TYPE OF ALBINISM



Richard A. King, M.D., Ph.D.
University of Minnesota Medical School
Hospital for Special Surgery and
Minneapolis, MN.

The identification of genes responsible for complex common diseases using automated linkage analysis and gene mapping techniques is a major area of emphasis for the laboratory.

Hermansky-Pudlak Syndrome is a genetic syndrome that presents with triad of oculocutaneous albinism, storage-pool deficient platelets and ceroid storage. The clinical problems in HPS are albinism associated with light skin/hair and reduced visual acuity, bleeding associated with the inability of the platelets to aggregate correctly, and pulmonary fibrosis and inflammatory bowel disease associated with the accumulation of ceroid in the tissues. HPS is rare in most areas of the would, but is found at a frequency greater than 1:2000 in Puerto Rico. The gene responsible for HPS in northwestern Puerto Rice (HPS1 gene) maps to chromosome 10 and we have isolated the gene, in collaboration with Murray Brilliant. The specific function of the gene product is unknown, but it is thought to be involved in intracellular protein trafficking and organelle formation, such as the melanosome in the pigment cell. A common founder mutation is responsible for the majority of cases of HPS1 in the Puerto Rican population, but there is evidence for genetic heterogeneity with another type of HPS being present on this island. Studies are underway to identify the second HPS gene in this population. The mouse model of the chromosome 10 HPS gene is the pale ear (ep) mouse, and this gene has been isolated in collaboration with Murray Brilliant and Richard Swank, Ph.D., Roswell Park Cancer Institute. The phenotype of the pale ear mouse differs from that of HPS and knock-out/transgenic mouse analyses are now underway to determine the function of the HPS/ep gene product, and the function of the two transcripts. The most significant clinical problem in human albinism is the loss of visual acuity associated with deficient melanin in the developing eye and optic system. To address this problem, a program has been developed to evaluate the potential for gene therapy in the eye. Methods for inducing melanin synthesis in or delivering melanin synthesizing cells to the retinal pigment epithelium are being developed. A colony or tyrosinase deficient cats are being raised as the model system for this work.