Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification

Schwartzlow, Coreen; Kazamel, Mohamed

doi:10.1007/s11910-019-0974-3

Cited by 42 publications

(38 citation statements)

References 94 publications

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“…Hereditary sensory neuropathies (HSNs) are neurological disorders characterized by degeneration of sensory neurons, with distal sensory loss in the lower limbs. HSNs are classified in eight phenotypically diverse types, which relate to specific genomic mutations and inheritance pattern (Schwartzlow and Kazamel, 2019). Mutations associated to HSNs affect functionally heterogeneous genes, making difficult to find a common pathway affected in patients (Rotthier et al, 2012).…”

Section: Peripheral Neuropathies and Ermentioning

confidence: 99%

“…FAM134B is found at the cis-Golgi network, regulating the morphology of this structure (Kurth et al, 2009), but also at the membrane of perinuclear ER, where acts as a ER-phagy receptor, mediating ER sequestration into autophagosomes (Khaminets et al, 2015). The most common HSN is HSN type I, presenting a progressive autosomal dominant pattern of inheritance and causing a slowly progressive neuronal degeneration (Schwartzlow and Kazamel, 2019). HSN type I can be caused by mutations in SPTL1 or SPTL2 genes, which respectively encodes for subunits 1 and 2 of the enzyme serine palmitoyltransferase (SPT).…”

Section: Peripheral Neuropathies and Ermentioning

confidence: 99%

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Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

2020

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The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca 2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca 2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.

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Section: Peripheral Neuropathies and Ermentioning

confidence: 99%

Section: Peripheral Neuropathies and Ermentioning

confidence: 99%

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

2020

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“…Additionally, a phenotype of macular telangiectasia type 2 and peripheral neuropathy may occur when the level of serine in patients is low for a long time, 7 elevating these potential risks of serine restriction treatment. Moreover, a neurotoxicity of 1‐deoxysphingolipids raised by the expression of SPT variants, SPTLC1 and SPTLC2 , also could account for rare autosomal dominant disorder, hereditary sensory and autonomic neuropathy type 1 (HSAN1) 8 . Thus, it is necessary to decode the mechanisms of how the molecular switch SPT selectively binds to different amino acid substrates and how these deoxysphingolipids exert cytotoxicity in the future work.…”

Section: Figurementioning

confidence: 99%

Modulating serine palmitoyltransferase‐deoxysphingolipid axis in cancer therapy

Xiang

Zhao

Tang

et al. 2020

MedComm

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A schematic illustration is given regarding serine restriction on tumor growth. Once the cellular abundance of serine decreased or alanine accumulated, the serine palmitoyltransferase (SPT) alternatively conjugates alanine and palmitoyl‐CoA to form 3‐keto‐intermediates, which is rapidly converted to 1‐deoxysphinganine and further metabolized to 1‐deoxydihydroceramide (1‐DeoxyDHCER) and 1‐deoxyceramide (1‐DeoxyDHCER), so that to exert cytotoxicity for tumor suppression.

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“…4 Mutations in the FAM134B gene, also known as RETREG1 gene, are associated to the subtype HSAN-IIB. 5 Here, we report the clinical findings of two non-related families carrying two novel homozygous mutations in the FAM134B gene.…”

mentioning

confidence: 93%

“…Although the subtypes are clinically very similar, there may be some mild distinguishable features . Mutations in the FAM134B gene, also known as RETREG1 gene, are associated to the subtype HSAN‐IIB …”

Section: Introductionmentioning

confidence: 99%

Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene

Campos

Vidailhet

Toutain

et al. 2019

J Peripheral Nervous Sys

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Hereditary sensory autonomic neuropathy (HSAN) type II is a rare, autosomal recessive, and early onset sensory neuropathy, characterized by severe and progressive sensation impairment, leading to ulcero‐mutilating complications. FAM134B gene, also known as RETREG1 gene, mutations have been reported to be associated to HSAN‐IIB. We report four patients from two unrelated families who developed during childhood a sensory axonal neuropathy with variable severity and pronounced nociception impairment. Complications such as recurrent ulcerations, osteomyelitis, and osteonecrosis leading to distal amputation were noticed. Dysautonomia was mild or even absent in our group of patients. Additionally, either clinical or neurophysiological motor impairment was not uncommon. Presence of upper motor neuron signs was also a distinctive feature in two related patients. After extensive workup, two novel homozygous mutations in the FAM134B gene were identified. This report expands the clinical and genetic spectrum of HSAN type II and emphasizes the phenotype variability even within the same family.

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Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification

Cited by 42 publications

References 94 publications

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

Modulating serine palmitoyltransferase‐deoxysphingolipid axis in cancer therapy

Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene

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