ORPHA: 231512, 79430; DO: 0060541;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q24 | Hermansky-Pudlak syndrome 3 | 614072 | Autosomal recessive | 3 | HPS3 | 606118 |
A number sign (#) is used with this entry because of evidence that Hermansky-Pudlak syndrome-3 (HPS3) is caused by homozygous or compound heterozygous mutation in the HPS3 gene (606118) on chromosome 3q24.
Hermansky-Pudlak syndrome-3 (HPS3) is characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Clinically, affected individuals have a bleeding diathesis, horizontal nystagmus, decreased vision and very mild pigment dilution of hair, skin, and irides (summary by Anikster et al., 2001).
For a phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (203300).
Hazelwood et al. (1997) ascertained 2 individuals with Hermansky-Pudlak syndrome from central Puerto Rico who lacked the 16-bp duplication in the HPS1 gene (604982.0001), exhibited significant amounts of normal-sized HPS1 gene mRNA by Northern blot analysis, and had haplotypes in the HPS1 region of chromosome 10 that were different from the haplotype of every 16-bp duplication patient. Moreover, these 2 individuals displayed no mutations in their HPS1 cDNA sequences. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. The findings appeared to indicate locus heterogeneity of this disorder in Puerto Rico, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.
By examining 6 families from Aibonito, Naranjito, and Barranquitas, rural towns south of San Juan, Anikster et al. (2001) identified a second genetic isolate of HPS in central Puerto Rico. Thirteen affected individuals had a bleeding diathesis, horizontal nystagmus, decreased vision, and very mild pigment dilution of hair, skin, and irides. The diagnosis of HPS was confirmed by demonstrating an absence of platelet-dense bodies by wet-mount electron microscopy. All patients lacked the 16-bp duplication in HPS1.
The transmission pattern of HPS3 in the families studied by Anikster et al. (2001) was consistent with autosomal recessive inheritance.
By homozygosity mapping on pooled DNA of 6 families from central Puerto Rico with HPS, Anikster et al. (2001) localized the HPS3 gene to a 1.6-cM interval on chromosome 3q24.
Anikster et al. (2001) identified a homozygous mutation in the HPS3 gene (606118.0001) on chromosome 3q24 in families within central Puerto Rico, some members of which had been studied by Hazelwood et al. (1997). They stated that this was the second example of a founder mutation causing HPS in central Puerto Rico. They estimated that the large deletion in the HPS3 gene arose between 1880 and 1890. At that time the ancestors of 3 of the 6 HPS3 families emigrated from the town of Ciales to the towns of Aibonito, Barranquitas, and Naranjito. Each of the 3 families also traced its ancestry to 1 individual, Calixto Rivera, who brought his relatives to Aibonito and the surrounding area to deforest his land for tobacco growing.
Anikster, Y., Huizing, M., White, J., Shevchenko, Y. O., Fitzpatrick, D. L., Touchman, J. W., Compton, J. G., Bale, S. J., Swank, R. T., Gahl, W. A., Toro, J. R. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Nature Genet. 28: 376-380, 2001. [PubMed: 11455388] [Full Text: https://doi.org/10.1038/ng576]
Hazelwood, S., Shotelersuk, V., Wildenberg, S. C., Chen, D., Iwata, F., Kaiser-Kupfer, M. I., White, J. G., King, R. A., Gahl, W. A. Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome. Am. J. Hum. Genet. 61: 1088-1094, 1997. [PubMed: 9345105] [Full Text: https://doi.org/10.1086/301611]