The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy

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Suriyanarayanan , S , Auranen , M , Toppila , J , Paetau , A , Shcherbii , M , Palin , E , Wei , Y , Lohioja , T , Schlotter-Weigel , B , Schoen , U , Abicht , A , Rautenstrauss , B , Tyynismaa , H , Walter , M C , Hornemann , T & Ylikallio , E 2016 , ' The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy ' NeuroMolecular Medicine , vol. 18 , no. 1 , pp. 81-90 . DOI: 10.1007/s12017-015-8379-1

Title: The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy
Author: Suriyanarayanan, Saranya; Auranen, Mari; Toppila, Jussi; Paetau, Anders; Shcherbii, Maria; Palin, Eino; Wei, Yu; Lohioja, Tarja; Schlotter-Weigel, Beate; Schoen, Ulrike; Abicht, Angela; Rautenstrauss, Bernd; Tyynismaa, Henna; Walter, Maggie C.; Hornemann, Thorsten; Ylikallio, Emil
Contributor: University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Department of Diagnostics and Therapeutics
University of Helsinki, Medicum
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programme for Molecular Neurology
Date: 2016-03
Number of pages: 10
Belongs to series: NeuroMolecular Medicine
ISSN: 1535-1084
URI: http://hdl.handle.net/10138/223887
Abstract: Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C > T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy.
Subject: Neuropathy
Hereditary sensory autonomic neuropathy
Serine palmitoyl-CoA transferase
Sphingolipid
SERINE PALMITOYLTRANSFERASE
GENETIC-VARIANTS
TYPE-1
MUTATIONS
DEOXYSPHINGOLIPIDS
BIOMARKERS
3112 Neurosciences
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