Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel <i>HPS6</i> missense variant

Han, Chen; O’Brien, Kevin; Coon, Lea M.; Majerus, Julie A.; Huryn, Laryssa A.; Haroutunian, Sara G.; Moka, Nagabhishek; Introne, Wendy J.; Macnamara, Ellen; Gahl, William A.; Malicdan, May Christine V.; Chen, Dong; Krishnan, Koyamangalath; Gochuico, Bernadette R.

doi:10.1002/ajmg.a.40514

Cited by 10 publications

(13 citation statements)

References 20 publications

(26 reference statements)

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“…Topical thrombin, administration of procoagulant drugs, or intravenous 1‐desamino‐8D‐arginine vasopressin may ameliorate or prevent bleeding. Platelet transfusion may also be used as prophylaxis or as a treatment for bleeding in individuals with HPS (Han et al, 2018; Minkin, Bertetti, Lindsey, & Bovino, 2015; Ozgur & Yilmaz, 2015; Van Avermaete, Muys, & Jacquemyn, 2016). Avoidance of aspirin products and nonsteroidal anti‐inflammatory drugs is recommended.…”

Section: Introductionmentioning

confidence: 99%

Hermansky–Pudlak syndrome: Mutation update

et al. 2020

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Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive multisystem disorders, each defined by the deficiency of a specific gene. HPS-associated genes encode components of four ubiquitously expressed protein complexes: Adaptor protein-3 (AP-3) and biogenesis of lysosome-related organelles complex-1 (BLOC-1) through -3. All individuals with HPS exhibit albinism and a bleeding diathesis; additional features occur depending on the defective protein complex. Pulmonary fibrosis is associated with AP-3 and BLOC-3 deficiency, immunodeficiency with AP-3 defects, and gastrointestinal symptoms are more prevalent and severe in BLOC-3 deficiency. Therefore, identification of the HPS subtype is valuable for prognosis, clinical management, and treatment options. The prevalence of HPS is estimated at 1-9 per 1,000,000. Here we summarize 264 reported and novel variants in 10 HPS genes and estimate that~333 Puerto Rican HPS subjects and~385 with other ethnicities are reported to date. We provide pathogenicity predictions for missense and splice site variants and list variants with high minor allele frequencies. Current cellular and clinical aspects of HPS are also summarized. This review can serve as a manifest for molecular diagnostics and genetic counseling aspects of HPS.

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Section: Introductionmentioning

confidence: 99%

Hermansky–Pudlak syndrome: Mutation update

et al. 2020

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“…Han и соавт. [13] описали 58-летнюю женщину с установленным диагнозом «синдром Германского-Пудлака, тип 6» с выраженным геморрагическим синдромом, тяжелыми меноррагиями и маточными кровотечениями вплоть до госпитализации в отделение интенсивной терапии, также отмечались выраженные желудочно-кишечные кровотечения [13]. При проведении колоноскопии у женщины диагностированы два полипа небольших размеров, удаление которых привело к развитию кишечного кровотечения.…”

Section: Discussionunclassified

Hermansky–Pudlak Syndrome Type 6 Accompanied with Bowel Vascular Malformation: Clinical Case

Журкова

Вашакмадзе

Suhanova

et al. 2021

Vopr. sovr. pediatr.

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Background. Hermansky–Pudlak syndrome type 6 is rare hereditary disease caused by pathogenic variants in base sequence, deletions, and insertions in the HPS6 gene encoding the transmembrane protein of the same name. This disease occurs with hemorrhagic syndrome, oculocutaneous albinism, and inflammatory bowel diseases (in some cases). The clinical picture of the disease, including the gastrointestinal tract pathology, has not been studied completely due to the syndrome rarity.Clinical case description. We would like to present the description of clinical case of the patient with Hermansky–Pudlak syndrome type 6 accompanied with bowel vascular malformation. The patient diagnosed with “oculocutaneous albinism” at the age of 4.5 has shown recurrent intestinal bleedings, blood hemoglobin concentration decrease to 45 g/l; platelet count, mean platelet volume and platelet distribution width remained within the reference values. Slight decrease of Quick’s value to 68% (normal range 70–120%) was revealed. The study of platelet morphology has revealed a decrease in the number of dense granules: < 3 in 25% platelets, < 6 — in 64%. Ultrasound investigation has revealed signs of vascular malformation in ascending colon: significant changes of diameter (widening) and shape of intestinal wall vessels. Molecular genetic analysis (NGS) has revealed the nucleotide variant c.1133T>G (p.Leu378Arg) in homozygous state in the HPS6 gene. The same variant in homozygous state was revealed in the younger proband sister who also had vascular changes in the ascending colon wall.Conclusion. Differential diagnosis of Germanic–Pudlak syndrome type 6 should be performed with other types of this syndrome as well as with syndrome and non-syndrome forms of oculocutaneous albinism. Molecular genetic confirmation of the diagnosis is suggested via massive parallel sequencing (NGS) methods (exome sequencing included) due to the rarity of Hermansky–Pudlak syndrome.

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“…The diagnosis of HPS is established in an individual with oculocutaneous albinism and an increased tendency to bleed or easy bruisability who has pathogenic biallelic variants in genes associated with HPS. Targeted genetic sequencing or next-generation sequencing is emerging as a method to identify genetic variants and diagnose HPS in patients with clinical manifestations of disease [34,47,62,100,101]. Platelet whole-mount electron microscopy demonstrating absent δ-granules is consistent with HPS [16,54,82,102,103].…”

Section: Diagnosismentioning

confidence: 99%

Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease

Yokoyama

Gochuico

2021

Eur Respir Rev

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Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.

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

Cited by 10 publications

References 20 publications

Hermansky–Pudlak syndrome: Mutation update

Hermansky–Pudlak syndrome: Mutation update

Hermansky–Pudlak Syndrome Type 6 Accompanied with Bowel Vascular Malformation: Clinical Case

Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease

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