Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F10%3A6336" target="_blank" >RIV/00064203:_____/10:6336 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/10:6336 RIV/00216224:14110/10:00052290

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I

Original language description

We screened the two other known subunits of SPT, SPTLC2 and SPTLC3, in a cohort of 78 HSAN patients No mutations were found in SPTLC3, but we identified three heterozygous missense mutations in the SPTLC2 subunit of with four families presenting with a typical HSAN-I phenotype We demonstrate that these mutations result in a partial to complete loss of SPT activity in vitro and in vivo Moreover, they cause the accumulation of the atypical and neurotoxic sphingoid metabolite I-deoxy-sphinganine Our findings extend the genetic heterogeneity in HSAN-I and enlarge the group of HSAN neuropathies associated with SPT defects. We further show that HSAN-I is consistently associated with an Increased formation of the neurotoxic 1-deoxysphinganine, suggesting a common pathomechanism for HSAN-I.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/NS10552" target="_blank" >NS10552: Analysis of the BSCL 2 gene and a clinical study among Czech patients with hereditary motor neuropathy.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2010

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

American Journal of Human Genetics

ISSN

0002-9297

e-ISSN

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Volume of the periodical

87

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

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UT code for WoS article

000283037600007

EID of the result in the Scopus database

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