Hereditary neuralgic amyotrophy in childhood caused by duplication within the <i>SEPT9</i> gene: A family study

Neubauer, Katharina; Boeckelmann, Doris; Koehler, Udo; Kracht, J; Kirschner, Janbernd; Pendziwiat, Manuela; Zieger, Barbara

doi:10.1002/cm.21479

Cited by 11 publications

(11 citation statements)

References 45 publications

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“…A patient with homozygous co-deletion of SEPT5 and GPIbβ, a subunit of the platelet adhesion receptor (GP)Ib-V-IX, presented dramatically reduced platelet α-granule and slightly reduced δ-granule secretion, evidence not observed in patients with only a GPIbβ deletion but normal SEPT5 expression ( Bartsch et al, 2011 ). Family members having a congenital pathogenic variant in the N-terminal region of the SEPT9 -gene suffer from a mild δ-granule secretion defect ( Neubauer et al, 2019 ). Bai et al demonstrated that the N-terminal domain of SEPT9 binds and bundles microtubules by interacting with β-tubulin.…”

Section: Septins In Plateletsmentioning

confidence: 99%

Role of Septins in Endothelial Cells and Platelets

Neubauer

Zieger

2021

Front. Cell Dev. Biol.

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Septins are conserved cytoskeletal GTP-binding proteins identified in almost all eukaryotes except higher plants. Mammalian septins comprise 13 family members with either ubiquitous or organ- and tissue-specific expression patterns. They form filamentous oligomers and complexes with other proteins to serve as diffusions barrier and/or multi-molecular scaffolds to function in a physiologically regulated manner. Diverse septins are highly expressed in endothelial cells and platelets, which play an important role in hemostasis, a process to prevent blood loss after vascular injury. Endothelial septins are involved in cellular processes such as exocytosis and in processes concerning organismal level, like angiogenesis. Septins are additionally found in endothelial cell-cell junctions where their presence is required to maintain the integrity of the barrier function of vascular endothelial monolayers. In platelets, septins are important for activation, degranulation, adhesion, and aggregation. They have been identified as mediators of distinct platelet functions and being essential in primary and secondary hemostatic processes. Septin-knockout mouse studies show the relevance of septins in several aspects of hemostasis. This is in line with reports that dysregulation of septins is clinically relevant in human bleeding disorders. The precise function of septins in the biology of endothelial cells and platelets remains poorly understood. The following mini-review highlights the current knowledge about the role of septin cytoskeleton in regulating critical functions in these two cell types.

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Section: Septins In Plateletsmentioning

confidence: 99%

Role of Septins in Endothelial Cells and Platelets

Neubauer

Zieger

2021

Front. Cell Dev. Biol.

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“…Interestingly, we found a mild δ-granule secretion defect in a family with hereditary neuralgic amyotrophy and a pathogenic variation in the SEPT9 gene. 31 Different septins may cause different granule secretion defects, because the Sept8 À/À mouse in this study showed a selective defect in αgranule but not in δ-granule and lysosomal secretion.…”

Section: Discussionmentioning

confidence: 76%

Impaired Platelet Function in Sept8-Deficient Mice In Vitro

et al. 2020

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Septins (Septs) are a widely expressed protein family of 13 mammalian members, recognized as a unique component of the cytoskeleton. In human platelets, we previously described that SEPT4 and SEPT8 are localized surrounding α-granules and move to the platelet surface after activation, indicating a possible role in platelet physiology. In this study, we investigated the impact of Sept8 on platelet function in vitro using Sept8-deficient mouse platelets. Deletion of Sept8 in mouse platelets caused a pronounced defect in activation of the fibrinogen receptor integrin αIIbβ3, α-granule exocytosis, and aggregation, especially in response to the glycoprotein VI agonist convulxin. In contrast, δ-granule and lysosome exocytosis of Sept8-deficient platelets was comparable to wild-type platelets. Sept8-deficient platelet binding to immobilized fibrinogen under static conditions was diminished and spreading delayed. The procoagulant activity of Sept8-deficient platelets was reduced in response to convulxin as determined by lactadherin binding. Also thrombin generation was decreased relative to controls. Thus, Sept8 is required for efficient integrin αIIbβ3 activation, α-granule release, platelet aggregation, and contributes to platelet-dependent thrombin generation. These results revealed Sept8 as a modulator of distinct platelet functions involved in primary and secondary hemostatic processes.

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“…Genetically, two missense mutations in the SEPT9 gene (1 of 13 proteins that has the function to form higher molecular structures and are involved in biological processes such as cytoskeleton formation) was found in cases of hereditary NA from Europe and North America 5,6 .…”

Section: Pathophysiologymentioning

confidence: 99%

Neuralgic Amyotrophy: Its Importance in Orthopedics Practice

Firmino

Schulze

Schlindwein

et al. 2021

Spine Surg Relat Res

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The present academic work aims to contribute to an early diagnosis of neuralgic amyotrophy (NA) because of its high prevalence in the population. This disease is a neuromuscular syndrome with unclear etiology; it affects mostly the brachial plexus, causing acute pain in the affected shoulder, paralysis, and disabilities. Considering the importance of an early treatment that can modify the prognosis of the patient, knowing the last updates about the syndrome as its clinical presentation is important. Data analysis was conducted through an online non-systematic review that indicated the epidemiology, pathophysiology, and differential diagnosis and prognosis of NA. Knowledge of the clinical features of NA is not common; however, it is important in orthopedic practice because it requires differentiation from spine pathologies.

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Hereditary neuralgic amyotrophy in childhood caused by duplication within the SEPT9 gene: A family study

Cited by 11 publications

References 45 publications

Role of Septins in Endothelial Cells and Platelets

Role of Septins in Endothelial Cells and Platelets

Impaired Platelet Function in Sept8-Deficient Mice In Vitro

Neuralgic Amyotrophy: Its Importance in Orthopedics Practice

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