Human BCL10 Deficiency due to Homozygosity for a Rare Allele.

Autor: Van Den Rym A; Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Interdepartmental Group of Immunodeficiencies, Madrid, Spain., Taur P; Division of Immunology, Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, 400012, India., Martinez-Barricarte R; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, 10065, USA., Lorenzo L; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, 75015, Paris, France., Puel A; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, 10065, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, 75015, Paris, France.; Imagine Institute, University Paris Descartes, 75015, Paris, France., Gonzalez-Navarro P; Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Interdepartmental Group of Immunodeficiencies, Madrid, Spain., Pandrowala A; Division of Immunology, Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, 400012, India., Gowri V; Division of Immunology, Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, 400012, India., Safa A; Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Interdepartmental Group of Immunodeficiencies, Madrid, Spain.; Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, 28040, Madrid, Spain., Toledano V; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain., Cubillos-Zapata C; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain.; Center for Biomedical Research Network, CIBEres, Madrid, Spain., López-Collazo E; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain., Vela M; Translational Research in Paediatric Oncology, Haematopoietic Stem Cell Transplantation, Cell Therapy, INGEMM-IdiPAZ, La Paz University Hospital, Madrid, Spain., Pérez-Martínez A; Translational Research in Paediatric Oncology, Haematopoietic Stem Cell Transplantation, Cell Therapy, INGEMM-IdiPAZ, La Paz University Hospital, Madrid, Spain.; Department of Paediatric Haemato-oncology and Stem Cell Transplantation, La Paz University Hospital, Madrid, Spain., Sánchez-Ramón S; Interdepartmental Group of Immunodeficiencies, Madrid, Spain.; Clinical Immunology Department, San Carlos Clinical Hospital, 28040, Madrid, Spain., Recio MJ; Interdepartmental Group of Immunodeficiencies, Madrid, Spain.; Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, 28040, Madrid, Spain., Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, 10065, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, 75015, Paris, France.; Imagine Institute, University Paris Descartes, 75015, Paris, France.; Paediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015, Paris, France.; Howard Hughes Medical Institute, New York, NY, 10065, USA., Desai MM; Division of Immunology, Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, 400012, India., Perez de Diego R; Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain. rebeca.perez@idipaz.es.; Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, 28046, Madrid, Spain. rebeca.perez@idipaz.es.; Interdepartmental Group of Immunodeficiencies, Madrid, Spain. rebeca.perez@idipaz.es.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2020 Feb; Vol. 40 (2), pp. 388-398. Date of Electronic Publication: 2020 Feb 01.
DOI: 10.1007/s10875-020-00760-3
Abstrakt: In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), previously reported as a rare allele in heterozygosis (minor allele frequency, 0.000003986). The mutant allele was a loss-of-expression and loss-of-function allele. As with the previously reported patient, this patient had complete BCL10 deficiency. The clinical phenotype shared features, such as respiratory infections, but differed from that of the previous patient that he did not develop significant gastroenteritis episodes or chronic colitis. Cellular and immunological phenotypes were similar to those of the previous patient. TLR4, TLR2/6, and Dectin-1 responses were found to depend on BCL10 in fibroblasts, and final maturation of T cell and B cell maturation into memory cells was affected. Autosomal-recessive BCL10 deficiency should therefore be considered in children with CID.
Databáze: MEDLINE
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