Hermansky-Pudlak Syndrome 5
A number sign (#) is used with this entry because of evidence that Hermansky-Pudlak syndrome-5 (HPS5) is caused by homozygous mutation in the HPS5 gene (607521) on chromosome 11p14.
DescriptionHermansky-Pudlak syndrome-5 (HPS5) is characterized by oculocutaneous albinism, a bleeding diathesis, and lack of platelet dense bodies. HPS5 appears to be a milder form of the syndrome because the complications present in other forms of HPS, such as pulmonary fibrosis, granulomatous colitis, and neutropenia, have not been reported in HPS5 patients (Ringeisen et al., 2013).
For a general phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (203300).
Clinical FeaturesZhang et al. (2003) described a patient with Hermansky-Pudlak syndrome who had a mutation in the HPS5 gene (see MOLECULAR GENETICS). The 3-year-old Turkish boy, whose parents were first cousins, had clinically mild oculocutaneous albinism and easy bruising. His platelet count was moderately reduced, and his bleeding time was moderately prolonged.
Huizing et al. (2004) described 4 patients with HPS5, 2 of whom were sisters. All 4 patients exhibited typical HPS findings, including reduced visual acuity, nystagmus, iris transillumination, variable hair and skin pigmentation, easy bruising, and absent platelet dense bodies. Epistaxis occurred in 2 patients, and 2 of the 3 women reported menorrhagia; in addition, 1 woman underwent partial hysterectomy for bleeding fibroids. None of the patients displayed evidence of colitis or pulmonary fibrosis, but Huizing et al. (2004) noted that 2 of the patients were less than 27 years old, the age before which lung disease rarely develops in any type of HPS. In addition, serum cholesterol levels were elevated in all 4 patients, as were triglyceride levels in 3 of them; the authors suggested that this might be related to abnormal trafficking of cholesterol-containing vesicles within cells.
Ringeisen et al. (2013) reported a 92-year-old man with HPS who presented at age 72 due to prolonged bleeding after bladder tumor resection. He had white hair at birth that became light brown during childhood, as well as lifelong reduced visual acuity and horizontal nystagmus. In addition, funduscopy had previously shown a blonde fundus, foveal hypoplasia, and translucent irides, consistent with oculocutaneous albinism. He had a history of excessive bleeding after tonsillectomy at age 13 and required cauterization to stop a nosebleed in his 20s; electron microscopy showed that his platelets lacked dense bodies, confirming the clinical diagnosis of HPS. At age 92, his visual acuity was hand motion on the right and light perception on the left, and he had dense nuclear sclerotic cataracts as well as large macular staphylomas bilaterally. He did not report pulmonary or gastrointestinal disease, but noted steroid treatment for 'colitis' in middle age, although he was currently asymptomatic.
Stephen et al. (2017) studied a 27-year-old Turkish man with mild hypopigmentation, nystagmus, and impaired visual acuity, who also had easy bruising, prolonged bleeding after dental extractions, and a history of nosebleeds. His parents were first cousins, and some family members also exhibited albinism, including his sister, paternal uncle, and several first cousins. Ophthalmologic examination showed iris transillumination, minimal retinal pigmentation, and peripapillary atrophy. Optical coherence tomography (OCT) was consistent with foveal hypoplasia, and visual evoked potential testing revealed the crossing changes typical of albinism. Electron microscopy of platelets showed absent delta granules (dense bodies). Although the patient did not show clinical signs of pulmonary disease, analysis of bronchoalveolar lavage cells revealed foamy alveolar macrophages resembling those seen in patients with HPS1, who are at high risk for pulmonary fibrosis. Stephen et al. (2017) noted that foamy macrophages might represent a response to a profibrotic alveolar milieu, and suggested that patients with HPS5 should be followed for possible lung disease.
MappingZhang et al. (2003) mapped the HPS5 gene to chromosome 11p15-p13.
Molecular GeneticsIn a 3-year-old Turkish boy with HPS, Zhang et al. (2003) identified a homozygous 4-bp deletion (607521.0001) in the HPS5 gene.
In 15 patients with HPS who did not exhibit neutropenia (see HPS2, 608233) and were negative for mutation in 3 HPS-associated genes, Huizing et al. (2004) screened for mutations in the HPS5 gene and identified homozygous and compound heterozygous variants in 4 of the patients (see, e.g., 607521.0002-607521.0004). Two of the patients with HPS5 mutations were sisters who were homozygous for 2 different missense variants; the authors noted that it was unlikely that 2 disease-causing mutations would be present on the same allele, and suggested that 1 of them might represent a polymorphism.
Ringeisen et al. (2013) screened genomic DNA from a 92-year-old man with HPS for mutations in known HPS-associated genes and identified homozygosity for a 1-bp deletion in the HPS5 gene (607521.0006).
In a 27-year-old Turkish man with HPS, Stephen et al. (2017) screened genes associated with cutaneous hypopigmentation and identified homozygosity for an intronic mutation in the HPS5 gene (607521.0007).