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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
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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. |
format | Online Article Text |
id | pubmed-4284369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
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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