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The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and...

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Autores principales: Sinkiewicz-Darol, Elena, Lacerda, Andressa Ferreira, Kostera-Pruszczyk, Anna, Potulska-Chromik, Anna, Sokołowska, Beata, Kabzińska, Dagmara, Brunetti, Craig R., Hausmanowa-Petrusewicz, Irena, Kochański, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284369/
https://www.ncbi.nlm.nih.gov/pubmed/25342198
http://dx.doi.org/10.1007/s10048-014-0426-9
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author Sinkiewicz-Darol, Elena
Lacerda, Andressa Ferreira
Kostera-Pruszczyk, Anna
Potulska-Chromik, Anna
Sokołowska, Beata
Kabzińska, Dagmara
Brunetti, Craig R.
Hausmanowa-Petrusewicz, Irena
Kochański, Andrzej
author_facet Sinkiewicz-Darol, Elena
Lacerda, Andressa Ferreira
Kostera-Pruszczyk, Anna
Potulska-Chromik, Anna
Sokołowska, Beata
Kabzińska, Dagmara
Brunetti, Craig R.
Hausmanowa-Petrusewicz, Irena
Kochański, Andrzej
author_sort Sinkiewicz-Darol, Elena
collection PubMed
description Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders.
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spelling pubmed-42843692015-01-12 The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases Sinkiewicz-Darol, Elena Lacerda, Andressa Ferreira Kostera-Pruszczyk, Anna Potulska-Chromik, Anna Sokołowska, Beata Kabzińska, Dagmara Brunetti, Craig R. Hausmanowa-Petrusewicz, Irena Kochański, Andrzej Neurogenetics Original Article Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders. Springer Berlin Heidelberg 2014-10-24 2015 /pmc/articles/PMC4284369/ /pubmed/25342198 http://dx.doi.org/10.1007/s10048-014-0426-9 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article
Sinkiewicz-Darol, Elena
Lacerda, Andressa Ferreira
Kostera-Pruszczyk, Anna
Potulska-Chromik, Anna
Sokołowska, Beata
Kabzińska, Dagmara
Brunetti, Craig R.
Hausmanowa-Petrusewicz, Irena
Kochański, Andrzej
The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title_full The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title_fullStr The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title_full_unstemmed The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title_short The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases
title_sort litaf/simple i92v sequence variant results in an earlier age of onset of cmt1a/hnpp diseases
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284369/
https://www.ncbi.nlm.nih.gov/pubmed/25342198
http://dx.doi.org/10.1007/s10048-014-0426-9
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