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. 1997 Nov;61(5):1088–1094. doi: 10.1086/301611

Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome.

S Hazelwood 1, V Shotelersuk 1, S C Wildenberg 1, D Chen 1, F Iwata 1, M I Kaiser-Kupfer 1, J G White 1, R A King 1, W A Gahl 1
PMCID: PMC1716022  PMID: 9345105

Abstract

Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis. In a recent report on the cloning of an HPS gene, all 22 Puerto Rican HPS patients were homozygous for a 16-bp duplication in exon 15. This presumably reflected a founder effect for the HPS mutation in Puerto Rico. Nevertheless, we ascertained two individuals from central Puerto Rico who lacked the 16-bp duplication, exhibited significant amounts of normal-size HPS mRNA by northern blot analysis, and had haplotypes in the HPS region that were different from the haplotype of every 16-bp-duplication patient. Moreover, these two individuals displayed no mutations in their cDNA sequences, throughout the entire HPS gene. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, a bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. These findings indicate that analysis of Puerto Rican patients for the 16-bp duplication in HPS cannot exclude the diagnosis of HPS. In addition, HPS most likely displays locus heterogeneity, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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