A number sign (#) is used with this entry because of evidence that Hermansky-Pudlak syndrome-11 (HPS11) is caused by homozygous mutation in the BLOC1S5 gene (607289) on chromosome 6p24.

Hermansky-Pudlak syndrome-11 (HPS11) is characterized by mild oculocutaneous albinism in association with a moderate bleeding diathesis. Patients lack detectable platelet dense granules, and show mildly impaired activation-induced ATP release and platelet aggregation in vitro (Pennamen et al., 2020).

For a general phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (203300).

Pennamen et al. (2020) reported 2 unrelated women with mild oculocutaneous albinism and a bleeding diathesis. Patient 1 was a 20-year-old French woman, diagnosed at age 2 months, who had creamy skin and blond hair that were lighter than those of other members of her family. Ocular features included nystagmus, reduced visual acuity (20/40 and 20/50), iris transillumination, retinal hypopigmentation with increased visibility of choroid vessels, and foveal hypoplasia. Mild signs of bleeding diathesis were not mentioned initially by the patient, but were elicited by history to include easy bruising, week-long episodes of epistaxis once or twice a year, and gingival bleeding. Platelet aggregation in response to a low concentration of collagen was reduced and delayed in the patient compared to controls, with increased latency, reduced velocity, and reduced maximal amplitude. However, platelet response to a high concentration of collagen and to other agonists was normal, consistent with a mild defect in dense granule secretion. Lumiaggregometry assay showed low ATP release after thrombin receptor (187930) agonist peptide (TRAP) activation, and HPLC revealed very low platelet serotonin storage. Whole-mount electron microscopy of patient platelets showed almost no dense granules compared to control. Patient 2 was a 39-year-old woman born to nonconsanguineous parents originating from the same village in Slovenia; she had yellow skin and platinum white hair at birth, although both parents had black hair. Examination showed pigmented skin, blond hair, brown irides, and numerous pigmented nevi. Features of mild ocular albinism included nystagmus, strabismus, photophobia, visual acuity of 20/33 bilaterally, iris transillumination, low-grade retinal hypopigmentation, optic nerve decussation anomalies on visual evoked potentials, and normal fovea. She had significant epistaxis in childhood, easy or unexplained bruising, menorrhagia improved by contraception, and excessive blood loss after childbirth, surgery, and dental extraction; she also reported recurrent infections, including pneumonia, herpes, and conjunctivitis. Platelet analysis was compatible with a quantitative defect of dense bodies.

The transmission pattern of HPS11 in the families reported by Pennamen et al. (2020) was consistent with autosomal recessive inheritance.

Pennamen et al. (2020) screened the genomes of 230 undiagnosed patients with albinism for variants in candidate genes and identified 2 unrelated women with mild oculocutaneous albinism and a bleeding diathesis who were homozygous for deletions in the BLOC1S5 gene (607289.0001 and 607289.0002, respectively). The unaffected parents of patient 1 were heterozygous for the proband's deletion; DNA was unavailable from family members of patient 2.