SLFN14-related thrombocytopenia: identification within a large series of patients with inherited thrombocytopenia

Marconi, Caterina; Buduo, Christian A. Di; Barozzi, Serena; Palombo, Flavia; Pardini, Simonetta; Zaninetti, Carlo; Pippucci, Tommaso; Noris, Patrizia; Balduini, Alessandra; Seri, Marco; Pecci, Alessandro

doi:10.1160/th15-11-0884

Cited by 29 publications

(34 citation statements)

References 15 publications

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“…22,48 Similar observations can be made for SFLN14, where all variants are located in the ATPase-AAA-4 domain, and rare variants outside this domain seem not to result in an IPD. 54 There are publicly accessible databases such as ClinVar, 94 DECIPHER, 95 and Exome variant server 96 and access-for-a-fee databases such as the Human Gene Mutation Database (HGMD) 97 that record disease-associated variants. HGMD maintains a catalog of high-penetrance variants derived from the literature.…”

Section: Assigning Pathogenicity To Novel Variants: Use Of Public Datmentioning

confidence: 99%

“…Although the mechanism is not clear, a defect in platelet formation was observed. 53,54 Finally, Quebec platelet disorder, thus far confined to French Canadians, is caused by a tandem duplication in PLAU, leading to overexpression of urokinase, and is characterized by thrombocytopenia, degradation of a-granule contents with normal granule structure, decreased aggregation in response to epinephrine, and lateonset bleeding. 55 …”

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confidence: 99%

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Inherited platelet disorders: toward DNA-based diagnosis

Lentaigne

Freson

Laffan

et al. 2016

Blood

119

101

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Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).1 The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein–protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management.

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Section: Assigning Pathogenicity To Novel Variants: Use Of Public Datmentioning

confidence: 99%

mentioning

confidence: 99%

Inherited platelet disorders: toward DNA-based diagnosis

Lentaigne

Freson

Laffan

et al. 2016

Blood

119

101

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“…Moreover, mechanisms that regulate ribosome availability in anucleate blood lineages have not been identified, though autophagy (Kundu et al, 2008), ubiquitin-dependent degradation (Etlinger and Goldberg, 1977; Wefes et al, 1995), as well as specific ribonucleases (Pisareva et al, 2015; Valentine et al, 1974) have been proposed to degrade ribosomes in reticulocytes. Delayed ribosome clearance is associated with abnormal erythroid maturation (Kundu et al, 2008; Valentine et al, 1974) and platelet dysfunction in humans (Fletcher et al, 2015; Marconi et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets

et al. 2016

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Summary Protein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from both anucleate lineages by ribosome profiling and uncover dramatic accumulation of post-termination, unrecycled ribosomes in the 3´UTRs of mRNAs. We demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation. Induction of ribosome rescue factors PELO and HBS1L is required to support protein synthesis when ABCE1 levels fall. including for hemoglobin production during blood cell development. Our observations suggest that this distinctive loss of ABCE1 in anucleate blood lineages could sensitize them to defects in ribosome homeostasis, perhaps explaining in part why genetic defects in the fundamental process of ribosome production (“ribosomopathies”) often affect hematopoiesis specifically.

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“…19,20 These observations suggest that platelets use a different ribosome clearance mechanism than reticulocytes.…”

Section: Introductionmentioning

confidence: 99%

Slowed decay of mRNAs enhances platelet specific translation

Mills

Green

Ingolia

2017

Blood

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SLFN14-related thrombocytopenia: identification within a large series of patients with inherited thrombocytopenia

Abstract: Supplementary Material to this article is available online at www.thrombosis-online.com.

Cited by 29 publications

References 15 publications

Inherited platelet disorders: toward DNA-based diagnosis

Inherited platelet disorders: toward DNA-based diagnosis

Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets

Slowed decay of mRNAs enhances platelet specific translation

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