Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype of respiratory infections.
Antibody deficiencies can be caused by a variety of defects that interfere with B-cell development, maturation, and/or function. Using whole-exome sequencing we found a PIK3R1 mutation in a patient with hypogammaglobulinemia and a narrow clinical phenotype of respiratory infections. Early diagnosis is crucial; careful analysis of B and T-cells followed by genetic analyses may help to distinguish activated PI3K-delta syndrome (APDS) from other, less severe, predominantly antibody deficiencies.
Clinical Immunology Department, Hospital Universitario de G.C. Dr. Negrín, Gran Canaria, Spain.
María Teresa
MT
Martínez-Saavedra
Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Department of Immunology, Complutense University School of Medicine, Hospital 12 de Octubre Health Research Institute, Madrid, Spain.
Sonia
S
García-Gomez
Clinical Immunology Department, Hospital Universitario de G.C. Dr. Negrín, Gran Canaria, Spain.
Ana
A
Domínguez Acosta
Clinical Immunology Department, Hospital Universitario de G.C. Dr. Negrín, Gran Canaria, Spain.
Juan Jesús
JJ
Mendoza Quintana
Infectious diseases Unit-Pediatrics Complejo Hospitalario Universitario Insular-Materno Infantil, Gran Canaria, Spain.
Jesús Poch
JP
Páez
Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Department of Immunology, Complutense University School of Medicine, Hospital 12 de Octubre Health Research Institute, Madrid, Spain.
Eduardo J
EJ
García-Reino
Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Department of Immunology, Complutense University School of Medicine, Hospital 12 de Octubre Health Research Institute, Madrid, Spain.
Gracián
G
Camps
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA.
Rubén
R
Martinez-Barricarte
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA.
Yuval
Y
Itan
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University Paris Descartes, Imagine Institute, Paris, France.
Bertrand
B
Boisson
Clinical Immunology Department, San Carlos Clinical Hospital, Madrid, Spain.
Silvia
S
Sánchez-Ramón
Department of Immunology, Complutense University School of Medicine, Hospital 12 de Octubre Health Research Institute, Madrid, Spain.
José Ramón
JR
Regueiro
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA; Howard Hughes Medical Institute, New York, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University Paris Descartes, Imagine Institute, Paris, France; Paediatric Haematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
Jean-Laurent
JL
Casanova
Clinical Immunology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain.
Carlos
C
Rodríguez-Gallego
Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain; Department of Immunology, Complutense University School of Medicine, Hospital 12 de Octubre Health Research Institute, Madrid, Spain. Electronic address: perezdediegor@gmail.com.
Rebeca
R
Pérez de Diego
D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D058543:Class Ia Phosphatidylinositol 3-Kinase; D005260:Female; D006801:Humans; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D058543:Class Ia Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; C588001:PIK3R1 protein, human
APDS; Antibody deficiency; Immunophenotyping; PIK3R1; Whole-exome sequencing