Evidence map›Paper›PMID 21665000›Full record

ArticleAmerican journal of human genetics2011

A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9.

Andrew R Cullinane, James A Curry, Carmelo Carmona-Rivera, C Gail Summers, Carla Ciccone, Nicholas D Cardillo, Heidi Dorward, Richard A Hess, James G White, David Adams and 2 more

RetractedOpen access · bronzeAbstract readCase ReportsRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 105 citations in OpenAlex.

  1. Platelet δ-Storage Pool Disease: An Update.Journal of clinical medicine · 2020
    Review
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  14. Hermansky-Pudlak Syndrome.Clinics in chest medicine · 2016
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Andrew R CullinaneMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: andrew.cullinane@nih.gov.
James A CurryMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Carmelo Carmona-RiveraMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
C Gail SummersDepartments of Ophthalmology and Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Carla CicconeMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nicholas D CardilloMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Heidi DorwardMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Richard A HessMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
James G WhiteDepartment of Laboratory Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
David AdamsMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Intramural Office of Rare Diseases Research, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA.
Marjan HuizingMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
William A GahlMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Intramural Office of Rare Diseases Research, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA.
National Institutes of Health · USNational Human Genome Research Institute · USUniversity of Minnesota · US

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
Cell Biology of Metabolic DisordersZIAHG200322 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2014
$3.1M
Intramural NIH HHS
6 · The paper itself

Abstract

Hermansky-Pudlak Syndrome (HPS) is an autosomal-recessive condition characterized by oculocutaneous albinism and a bleeding diathesis due to absent platelet delta granules. HPS is a genetically heterogeneous disorder of intracellular vesicle biogenesis. We first screened all our patients with HPS-like symptoms for mutations in the genes responsible for HPS-1 through HPS-6 and found no functional mutations in 38 individuals. We then examined all eight genes encoding the biogenesis of lysosome-related organelles complex-1, or BLOC-1, proteins in these individuals. This identified a homozygous nonsense mutation in PLDN in a boy with characteristic features of HPS. PLDN is mutated in the HPS mouse model pallid and encodes the protein pallidin, which interacts with the early endosomal t-SNARE syntaxin-13. We could not detect any full-length pallidin in our patient's cells despite normal mRNA expression of the mutant transcript. We could detect an alternative transcript that would skip the exon that harbored the mutation, but we demonstrate that if this transcript is translated into protein, although it correctly localizes to early endosomes, it does not interact with syntaxin-13. In our patient's melanocytes, the melanogenic protein TYRP1 showed aberrant localization, an increase in plasma-membrane trafficking, and a failure to reach melanosomes, explaining the boy's severe albinism and establishing his diagnosis as HPS-9.

Indexed as

Carrier ProteinsCodon, NonsenseDNA Mutational AnalysisGenetic TestingHermanski-Pudlak SyndromeHumansInfantIntracellular Signaling Peptides and ProteinsLectinsMaleMelanocytesMembrane GlycoproteinsNerve Tissue ProteinsOxidoreductasesQa-SNARE ProteinsSNARE ProteinsBLOC1S1 protein, humanBLOC1S6 protein, humanBloc1s6 protein, mouseCarrier ProteinsCodon, NonsenseIntracellular Signaling Peptides and ProteinsLectinsMembrane GlycoproteinsNerve Tissue ProteinsOxidoreductasesQa-SNARE ProteinsSNARE ProteinsTYRP1 protein, human

Identifiers

PMID21665000
PMCPMC3113249
OpenAlexW2058514026

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.