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Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS)
OBJECTIVE: Mevalonate kinase (MVK) deficiency is a rare autosomal recessive auto-inflammatory disorder characterised by recurring episodes of fever associated with multiple non-specific inflammatory symptoms and caused by mutations in the MVK gene. The phenotypic spectrum is wide and depends mostly...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785531/ https://www.ncbi.nlm.nih.gov/pubmed/26977311 http://dx.doi.org/10.1136/rmdopen-2015-000196 |
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author | Messer, Laurent Alsaleh, Ghada Georgel, Philippe Carapito, Raphael Waterham, Hans R Dali-Youcef, Nassim Bahram, Siamak Sibilia, Jean |
author_facet | Messer, Laurent Alsaleh, Ghada Georgel, Philippe Carapito, Raphael Waterham, Hans R Dali-Youcef, Nassim Bahram, Siamak Sibilia, Jean |
author_sort | Messer, Laurent |
collection | PubMed |
description | OBJECTIVE: Mevalonate kinase (MVK) deficiency is a rare autosomal recessive auto-inflammatory disorder characterised by recurring episodes of fever associated with multiple non-specific inflammatory symptoms and caused by mutations in the MVK gene. The phenotypic spectrum is wide and depends mostly on the nature of the mutations. Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is a relatively mild presentation and predominantly associated with a c.1129G>A (p.V377I) mutation in the MVK gene. We report cases of two sisters homozygous for this mutation but exhibiting distinct (symptomatic vs asymptomatic) phenotypes. METHODS: Patient history was obtained; physical and clinical examination and laboratory tests were performed; lipopolysaccharide (LPS) response of peripheral blood mononuclear cells was quantified. RESULTS: Low MVK enzymatic activity is not necessarily associated with inflammatory symptoms. Increased inflammatory cytokine secretion in response to LPS is associated with symptomatic MVK deficiency. CONCLUSIONS: Individuals who are homozygous for the common p.V377I mutation in the MVK gene may not display the characteristic inflammatory episodes diagnostic of MKD and thus may be lost for correct and timely diagnosis. |
format | Online Article Text |
id | pubmed-4785531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47855312016-03-14 Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) Messer, Laurent Alsaleh, Ghada Georgel, Philippe Carapito, Raphael Waterham, Hans R Dali-Youcef, Nassim Bahram, Siamak Sibilia, Jean RMD Open Inflammatory Arthritis OBJECTIVE: Mevalonate kinase (MVK) deficiency is a rare autosomal recessive auto-inflammatory disorder characterised by recurring episodes of fever associated with multiple non-specific inflammatory symptoms and caused by mutations in the MVK gene. The phenotypic spectrum is wide and depends mostly on the nature of the mutations. Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is a relatively mild presentation and predominantly associated with a c.1129G>A (p.V377I) mutation in the MVK gene. We report cases of two sisters homozygous for this mutation but exhibiting distinct (symptomatic vs asymptomatic) phenotypes. METHODS: Patient history was obtained; physical and clinical examination and laboratory tests were performed; lipopolysaccharide (LPS) response of peripheral blood mononuclear cells was quantified. RESULTS: Low MVK enzymatic activity is not necessarily associated with inflammatory symptoms. Increased inflammatory cytokine secretion in response to LPS is associated with symptomatic MVK deficiency. CONCLUSIONS: Individuals who are homozygous for the common p.V377I mutation in the MVK gene may not display the characteristic inflammatory episodes diagnostic of MKD and thus may be lost for correct and timely diagnosis. BMJ Publishing Group 2016-03-07 /pmc/articles/PMC4785531/ /pubmed/26977311 http://dx.doi.org/10.1136/rmdopen-2015-000196 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Inflammatory Arthritis Messer, Laurent Alsaleh, Ghada Georgel, Philippe Carapito, Raphael Waterham, Hans R Dali-Youcef, Nassim Bahram, Siamak Sibilia, Jean Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title | Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title_full | Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title_fullStr | Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title_full_unstemmed | Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title_short | Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) |
title_sort | homozygosity for the v377i mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia d and periodic fever syndrome (hids) |
topic | Inflammatory Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785531/ https://www.ncbi.nlm.nih.gov/pubmed/26977311 http://dx.doi.org/10.1136/rmdopen-2015-000196 |
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