Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome

Ammann, Sandra; Schulz, Ansgar; Krägeloh‐Mann, Ingeborg; Dieckmann, Nele M. G.; Niethammer, K.; Fuchs, Sebastian; Eckl, Katja Martina; Plank, Roswitha; Werner, Roland; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Bank, Julia; Strauss, Anne; Bernuth, Horst von; Stadt, Udo zur; Grieve, Samantha; Griffiths, Gillian M.; Lehmberg, Kai; Hennies, Hans Christian; Ehl, Stephan

doi:10.1182/blood-2015-09-671636

Cited by 152 publications

(177 citation statements)

References 49 publications

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“…The genetics of the disease is also fairly well understood; 10 genes have been identified to date [OMIM #203300 http://omim.org/entry/203300] [18]. It therefore makes an ideal test case for this new diagnostic approach, as an unambiguous diagnosis can be made.…”

Section: Super-resolution Imaging Of Plateletsmentioning

confidence: 99%

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Super-resolution microscopy in the diagnosis of platelet granule disorders

Knight

Gomez

Cutler

2017

Expert Review of Hematology

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Introduction: Platelet granule deficiencies lead to bleeding disorders, but their specific diagnosis typically requires whole mount transmission electron microscopy, which is often not available and has a number of important limitations. We recently proposed the use of advanced forms of fluorescence microscopy – the so-called ‘super-resolution’ microscopies – as a possible solution.Areas covered: In this special report, we review the diagnosis of platelet granule deficiencies, and discuss how recent developments in fluorescence microscopy may be useful in improving diagnostic approaches to these and related disorders. In particular, we conclude that super-resolution fluorescence microscopy may have advantages over transmission electron microscopy in this application.Expert commentary: The value of the super-resolution microscopies has been amply demonstrated in research; however, their potential in diagnostic applications is ripe for further exploration. Hematology is a field particularly likely to benefit because of the relative simplicity of sample preparation. We anticipate that the costs of the necessary instrumentation will continue to fall rapidly, making these technologies widely accessible to clinicians.

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Section: Super-resolution Imaging Of Plateletsmentioning

confidence: 99%

“…However, as new loci are still being discovered [18] and the effects of mutations vary between individuals, determining phenotype as well as genotype will continue to be important for the foreseeable future.…”

Section: Future Prospectsmentioning

confidence: 99%

Super-resolution microscopy in the diagnosis of platelet granule disorders

Knight

Gomez

Cutler

2017

Expert Review of Hematology

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“…HPS is a group of phenotypically similar but genetically heterogeneous, autosomal recessive inherited disorders (Wei and Li 2013;Ammann et al, 2016). The common clinical features of HPS are hypopigmentation, reduced visual acuity, prolonged bleeding, and colitis.…”

Section: Introductionmentioning

confidence: 99%

“…The common clinical features of HPS are hypopigmentation, reduced visual acuity, prolonged bleeding, and colitis. In some cases, pulmonary fibrosis, neuronal defects or immune deficiency are also present, depending on the different subtypes (Wei and Li 2013;Ammann et al, 2016). These symptoms are caused by abnormalities in tissue-specific LROs.…”

Section: Introductionmentioning

confidence: 99%

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Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish

et al. 2018

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Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is characterized by oculocutaneous albinism and a deficiency of the platelet storage pool resulting from defective biogenesis of lysosome-related organelles (LROs). To date, ten HPS genes have been identified, three of which belong to the octamer complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex (BORC). Due to lethality at the early embryo stage in BLOS1 knockout mice, the function of BLOS1 in the above two complexes and whether it has a novel function are unclear. Here, we generated three zebrafish mutant lines with a BLOC-1 deficiency, in which melanin and silver pigment formation was attenuated as a result of mutation of bloc1s1, bloc1s2, and dtnbp1a, suggesting that they function in the same complex. In addition, mutations of bloc1s1 and bloc1s2 caused an accumulation of clusters of lysosomal vesicles at the posterior part of the tectum, representing a BORC-specific function in zebrafish. Moreover, bloc1s1 is highly expressed in the swimbladder during post-embryonic stages and is required for positively regulating the expression of the genes, which is known to govern surfactant production and lung development in mammals. Our study identified BLOS1 as a crucial regulator of the surfactant system. Thus, the zebrafish swimbladder might be an easy system to screen and study genetic modifiers that control surfactant production and homeostasis.

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Proteins required for vacuolar function are targets of lysine polyphosphorylation in yeast

et al. 2019

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Polyphosphates (polyP) are long chains of inorganic phosphates that can be attached to lysine residues of target proteins as a non-enzymatic post-translational modification. This modification, termed polyphosphorylation, may be particularly prevalent in bacterial and fungal species that synthesize and store large quantities of polyP. In this study, we applied a proven screening strategy to evaluate the polyphosphorylation status of over 200 candidate targets in the budding yeast S. cerevisiae. We report 8 new polyphosphorylated proteins that interact genetically and physically with a previously identified network of targets implicated in ribosome biogenesis. The expanded target network includes vacuolar proteins Prb1 and Apl5, whose modification with polyP suggests a model for feedback regulation of polyP synthesis, while raising additional questions regarding the location of polyphosphorylation in vivo.. CC-BY 4.0 International license a certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under

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Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome

Cited by 152 publications

References 49 publications

Super-resolution microscopy in the diagnosis of platelet granule disorders

Super-resolution microscopy in the diagnosis of platelet granule disorders

Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish

Proteins required for vacuolar function are targets of lysine polyphosphorylation in yeast

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