| ROTTHIER, Annelies, Michaela AUER-GRUMBACH, Katrien JANSSENS, Jonathan BAETS, Anke PENNO, Leonardo ALMEIDA-SOUZA, Kim VAN HOOF, An JACOBS, Els DE VRIENDT, Beate SCHLOTTER-WEIGEL, Wolfgang LÖSCHER, Petr VONDRÁČEK, Pavel SEEMAN, Peter DE JONGHE, Patrick VAN DIJCK, Albena JORDANOVA, Thorsten HORNEMANN a Vincent TIMMERMAN. Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I. The American Journal of Human Genetics. USA: CELL PRESS, 2010, roč. 87, č. 4, s. 513–522. ISSN 0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2010.09.010. |
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@article{938060,
author = {Rotthier, Annelies and AuerandGrumbach, Michaela and Janssens, Katrien and Baets, Jonathan and Penno, Anke and AlmeidaandSouza, Leonardo and Van Hoof, Kim and Jacobs, An and De Vriendt, Els and SchlotterandWeigel, Beate and Löscher, Wolfgang and Vondráček, Petr and Seeman, Pavel and De Jonghe, Peter and Van Dijck, Patrick and Jordanova, Albena and Hornemann, Thorsten and Timmerman, Vincent},
article_location = {USA},
article_number = {4},
doi = {http://dx.doi.org/10.1016/j.ajhg.2010.09.010},
keywords = {Mutations; SPTLC2; Subunit; Serine; Palmitoyltransferase; Cause Hereditary Sensory; Autonomic Neuropathy Type I},
language = {eng},
issn = {0002-9297},
journal = {The American Journal of Human Genetics},
title = {Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I},
url = {http://www.ncbi.nlm.nih.gov/Omim/},
volume = {87},
year = {2010}
}
TY - JOUR
ID - 938060
AU - Rotthier, Annelies - Auer-Grumbach, Michaela - Janssens, Katrien - Baets, Jonathan - Penno, Anke - Almeida-Souza, Leonardo - Van Hoof, Kim - Jacobs, An - De Vriendt, Els - Schlotter-Weigel, Beate - Löscher, Wolfgang - Vondráček, Petr - Seeman, Pavel - De Jonghe, Peter - Van Dijck, Patrick - Jordanova, Albena - Hornemann, Thorsten - Timmerman, Vincent
PY - 2010
TI - Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I
JF - The American Journal of Human Genetics
VL - 87
IS - 4
SP - 513–522
EP - 513–522
PB - CELL PRESS
SN - 00029297
KW - Mutations
KW - SPTLC2
KW - Subunit
KW - Serine
KW - Palmitoyltransferase
KW - Cause Hereditary Sensory
KW - Autonomic Neuropathy Type I
UR - http://www.ncbi.nlm.nih.gov/Omim/
N2 - Hereditary sensory and autonomic neuropathy type I (HSAN-I) is an axonal peripheral neuropathy associated with progressive distal sensory loss and severe ulcerations. Mutations in the first subunit of the enzyme serine palmitoyltransferase (SPT) have been associated with HSAN-I. The SPT enzyme catalyzes the first and rate-limiting step in the de novo sphingolipid synthesis pathway. However, different studies suggest the implication of other genes in the pathology of HSAN-I. Therefore, 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 SPT in 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 1-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.
ER -
ROTTHIER, Annelies, Michaela AUER-GRUMBACH, Katrien JANSSENS, Jonathan BAETS, Anke PENNO, Leonardo ALMEIDA-SOUZA, Kim VAN HOOF, An JACOBS, Els DE VRIENDT, Beate SCHLOTTER-WEIGEL, Wolfgang LÖSCHER, Petr VONDRÁČEK, Pavel SEEMAN, Peter DE JONGHE, Patrick VAN DIJCK, Albena JORDANOVA, Thorsten HORNEMANN a Vincent TIMMERMAN. Mutations in the SPTLC2 Subunit of Serine Palmitoyltransferase Cause Hereditary Sensory and Autonomic Neuropathy Type I. \textit{The American Journal of Human Genetics}. USA: CELL PRESS, 2010, roč.~87, č.~4, s.~513–522. ISSN~0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2010.09.010.
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