Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel HPS6 missense variant.

Autor: Han CG; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland., O'Brien KJ; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland., Coon LM; Division of Hematopathology, Mayo Clinic, Rochester, Minnesota., Majerus JA; Division of Hematopathology, Mayo Clinic, Rochester, Minnesota., Huryn LA; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland., Haroutunian SG; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland., Moka N; Division of Hematology-Oncology, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee., Introne WJ; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland., Macnamara E; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland., Gahl WA; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland., Malicdan MCV; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland., Chen D; Division of Hematopathology, Mayo Clinic, Rochester, Minnesota., Krishnan K; Division of Hematology-Oncology, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee., Gochuico BR; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2018 Dec; Vol. 176 (12), pp. 2819-2823. Date of Electronic Publication: 2018 Oct 04.
DOI: 10.1002/ajmg.a.40514
Abstrakt: Heřmanský-Pudlák syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS-6) is an uncommon subtype generally associated with mild disease. A Caucasian adult female presented with a history of severe bleeding; ophthalmologic examination indicated occult oculocutaneous albinism. The patient was diagnosed with a platelet storage pool disorder, and platelet whole mount electron microscopy demonstrated absent delta granules. Genome-wide SNP analysis showed regions of homozygosity that included the HPS1 and HPS6 genes. Full length HPS1 transcript was amplified by PCR of genomic DNA. Targeted next-generation sequencing identified a novel homozygous missense variant in HPS6 (c.383 T > C; p.V128A); this was associated with significantly reduced HPS6 mRNA and protein expression in the patient's fibroblasts compared to control cells. These findings highlight the variable severity of disease manifestations in patients with HPS, and illustrate that HPS can be diagnosed in patients with excessive bleeding and occult oculocutaneous albinism. Genetic analysis and platelet electron microscopy are useful diagnostic tests in evaluating patients with suspected HPS. Clinical Trial registration: Registrar: ClinicalTrials.gov Website: www.clinicaltrials.gov Registration Numbers: NCT00001456 and NCT00084305.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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