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A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases
We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency an...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Springer US
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086538/ https://www.ncbi.nlm.nih.gov/pubmed/31853824 http://dx.doi.org/10.1007/s10875-019-00731-3 |
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| author | Novice, Taylor Kariminia, Amina Del Bel, Kate L. Lu, Henry Sharma, Mehul Lim, Chinten J. Read, Jay Lugt, Mark Vander Hannibal, Mark C. O’Dwyer, David Hosler, Mirie Scharnitz, Thomas Rizzo, Jason M Zacur, Jennifer Priatel, John Abdossamadi, Sayeh Bohm, Alexandra Junker, Anne Turvey, Stuart E. Schultz, Kirk R. Rozmus, Jacob |
| author_facet | Novice, Taylor Kariminia, Amina Del Bel, Kate L. Lu, Henry Sharma, Mehul Lim, Chinten J. Read, Jay Lugt, Mark Vander Hannibal, Mark C. O’Dwyer, David Hosler, Mirie Scharnitz, Thomas Rizzo, Jason M Zacur, Jennifer Priatel, John Abdossamadi, Sayeh Bohm, Alexandra Junker, Anne Turvey, Stuart E. Schultz, Kirk R. Rozmus, Jacob |
| author_sort | Novice, Taylor |
| collection | PubMed |
| description | We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation. Expression of the altered p.(Met1141Lys) variant in a PLCγ2-knockout DT40 cell line showed clearly enhanced BCR-triggered influx of external calcium when compared to control-transfected cells. Our results further expand the molecular basis of pediatric CVID and phenotypic spectrum of PLCγ2-related defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-019-00731-3) contains supplementary material, which is available to authorized users. |
| format | Online Article Text |
| id | pubmed-7086538 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Springer US |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-70865382020-03-23 A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases Novice, Taylor Kariminia, Amina Del Bel, Kate L. Lu, Henry Sharma, Mehul Lim, Chinten J. Read, Jay Lugt, Mark Vander Hannibal, Mark C. O’Dwyer, David Hosler, Mirie Scharnitz, Thomas Rizzo, Jason M Zacur, Jennifer Priatel, John Abdossamadi, Sayeh Bohm, Alexandra Junker, Anne Turvey, Stuart E. Schultz, Kirk R. Rozmus, Jacob J Clin Immunol Original Article We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation. Expression of the altered p.(Met1141Lys) variant in a PLCγ2-knockout DT40 cell line showed clearly enhanced BCR-triggered influx of external calcium when compared to control-transfected cells. Our results further expand the molecular basis of pediatric CVID and phenotypic spectrum of PLCγ2-related defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-019-00731-3) contains supplementary material, which is available to authorized users. Springer US 2019-12-19 2020 /pmc/articles/PMC7086538/ /pubmed/31853824 http://dx.doi.org/10.1007/s10875-019-00731-3 Text en © Springer Science+Business Media, LLC, part of Springer Nature 2019 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
| spellingShingle | Original Article Novice, Taylor Kariminia, Amina Del Bel, Kate L. Lu, Henry Sharma, Mehul Lim, Chinten J. Read, Jay Lugt, Mark Vander Hannibal, Mark C. O’Dwyer, David Hosler, Mirie Scharnitz, Thomas Rizzo, Jason M Zacur, Jennifer Priatel, John Abdossamadi, Sayeh Bohm, Alexandra Junker, Anne Turvey, Stuart E. Schultz, Kirk R. Rozmus, Jacob A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title | A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title_full | A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title_fullStr | A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title_full_unstemmed | A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title_short | A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases |
| title_sort | germline mutation in the c2 domain of plcγ2 associated with gain-of-function expands the phenotype for plcg2-related diseases |
| topic | Original Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086538/ https://www.ncbi.nlm.nih.gov/pubmed/31853824 http://dx.doi.org/10.1007/s10875-019-00731-3 |
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