Cargando…
A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome
While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far,...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631694/ https://www.ncbi.nlm.nih.gov/pubmed/35404999 http://dx.doi.org/10.1182/bloodadvances.2021006789 |
_version_ | 1784823870684921856 |
---|---|
author | Marx, David Dupuis, Arnaud Eckly, Anita Molitor, Anne Olagne, Jérôme Touchard, Guy Kaaki, Sihem Ory, Cécile Faller, Anne-Laure Gérard, Bénédicte Cotter, Melanie Westerberg, Lisa Keszei, Marton Moulin, Bruno Gachet, Christian Caillard, Sophie Bahram, Seiamak Carapito, Raphaël |
author_facet | Marx, David Dupuis, Arnaud Eckly, Anita Molitor, Anne Olagne, Jérôme Touchard, Guy Kaaki, Sihem Ory, Cécile Faller, Anne-Laure Gérard, Bénédicte Cotter, Melanie Westerberg, Lisa Keszei, Marton Moulin, Bruno Gachet, Christian Caillard, Sophie Bahram, Seiamak Carapito, Raphaël |
author_sort | Marx, David |
collection | PubMed |
description | While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T>C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes. |
format | Online Article Text |
id | pubmed-9631694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-96316942022-11-04 A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome Marx, David Dupuis, Arnaud Eckly, Anita Molitor, Anne Olagne, Jérôme Touchard, Guy Kaaki, Sihem Ory, Cécile Faller, Anne-Laure Gérard, Bénédicte Cotter, Melanie Westerberg, Lisa Keszei, Marton Moulin, Bruno Gachet, Christian Caillard, Sophie Bahram, Seiamak Carapito, Raphaël Blood Adv Stimulus Report While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T>C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes. American Society of Hematology 2022-09-19 /pmc/articles/PMC9631694/ /pubmed/35404999 http://dx.doi.org/10.1182/bloodadvances.2021006789 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Stimulus Report Marx, David Dupuis, Arnaud Eckly, Anita Molitor, Anne Olagne, Jérôme Touchard, Guy Kaaki, Sihem Ory, Cécile Faller, Anne-Laure Gérard, Bénédicte Cotter, Melanie Westerberg, Lisa Keszei, Marton Moulin, Bruno Gachet, Christian Caillard, Sophie Bahram, Seiamak Carapito, Raphaël A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title | A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title_full | A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title_fullStr | A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title_full_unstemmed | A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title_short | A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome |
title_sort | gain-of-function variant in the wiskott-aldrich syndrome gene is associated with a myh9-related disease-like syndrome |
topic | Stimulus Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631694/ https://www.ncbi.nlm.nih.gov/pubmed/35404999 http://dx.doi.org/10.1182/bloodadvances.2021006789 |
work_keys_str_mv | AT marxdavid againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT dupuisarnaud againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT ecklyanita againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT molitoranne againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT olagnejerome againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT touchardguy againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT kaakisihem againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT orycecile againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT fallerannelaure againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT gerardbenedicte againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT cottermelanie againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT westerberglisa againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT keszeimarton againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT moulinbruno againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT gachetchristian againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT caillardsophie againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT bahramseiamak againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT carapitoraphael againoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT marxdavid gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT dupuisarnaud gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT ecklyanita gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT molitoranne gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT olagnejerome gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT touchardguy gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT kaakisihem gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT orycecile gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT fallerannelaure gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT gerardbenedicte gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT cottermelanie gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT westerberglisa gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT keszeimarton gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT moulinbruno gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT gachetchristian gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT caillardsophie gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT bahramseiamak gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome AT carapitoraphael gainoffunctionvariantinthewiskottaldrichsyndromegeneisassociatedwithamyh9relateddiseaselikesyndrome |