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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.
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.
  • Novice T; University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
  • Kariminia A; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Del Bel KL; Department of Pediatrics, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Lu H; Department of Pediatrics, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Sharma M; Department of Pediatrics, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Lim CJ; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Read J; Department of Pediatrics, Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
  • Lugt MV; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
  • Hannibal MC; Division of Pediatric Genetics, Metabolism & Genomic Medicine, Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
  • O'Dwyer D; Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Hosler M; Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI, USA.
  • Scharnitz T; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Rizzo JM; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Zacur J; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Priatel J; Department of Pediatrics, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Abdossamadi S; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Bohm A; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Junker A; Division of Clinical Immunology & Allergy, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
  • Turvey SE; Division of Clinical Immunology & Allergy, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
  • Schultz KR; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
  • Rozmus J; Division of Pediatric Hematology/Oncology and Bone Marrow Transplant, Department of Pediatrics, BC Children's Hospital, University of British Columbia, 4480 Oak Street, Vancouver, Canada.
J Clin Immunol ; 40(2): 267-276, 2020 02.
Article in English | MEDLINE | ID: covidwho-829366
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Common Variable Immunodeficiency / Germ-Line Mutation / Mutation, Missense / Phospholipase C gamma / Immunologic Deficiency Syndromes Type of study: Case report / Diagnostic study / Experimental Studies / Observational study Topics: Long Covid / Variants Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: English Journal: J Clin Immunol Year: 2020 Document Type: Article Affiliation country: S10875-019-00731-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Common Variable Immunodeficiency / Germ-Line Mutation / Mutation, Missense / Phospholipase C gamma / Immunologic Deficiency Syndromes Type of study: Case report / Diagnostic study / Experimental Studies / Observational study Topics: Long Covid / Variants Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: English Journal: J Clin Immunol Year: 2020 Document Type: Article Affiliation country: S10875-019-00731-3