TY - JOUR
T1 - Delayed diagnosis in X-linked agammaglobulinemia and its relationship to the occurrence of mutations in BTK non-kinase domains
AU - Carrillo-Tapia, Eduardo
AU - García-García, Elizabeth
AU - Herrera-González, Norma Estela
AU - Yamazaki-Nakashimada, Marco Antonio
AU - Staines-Boone, Aidee Tamara
AU - Segura-Mendez, Nora Hilda
AU - Scheffler-Mendoza, Selma Cecilia
AU - O‘Farrill-Romanillos, Patricia
AU - Gonzalez-Serrano, Maria E.
AU - Rodriguez-Alba, Juan Carloa
AU - Santos-Argumedo, Leopoldo
AU - Berron-Ruiz, Laura
AU - Sanchez-Flores, Alejandro
AU - López-Herrera, Gabriela
N1 - Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/1/2
Y1 - 2018/1/2
N2 - Background: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton’s Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. Methods: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. Results: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. Conclusions: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.
AB - Background: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton’s Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. Methods: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. Results: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. Conclusions: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.
KW - Bruton tyrosine kinase (BTK)
KW - Delayed X-linked agammaglobulinemia (XLA)
KW - PH and SH2 domains
KW - atypical phenotype
UR - http://www.scopus.com/inward/record.url?scp=85037707998&partnerID=8YFLogxK
U2 - 10.1080/1744666X.2018.1413349
DO - 10.1080/1744666X.2018.1413349
M3 - Artículo
C2 - 29202590
SN - 1744-666X
VL - 14
SP - 83
EP - 93
JO - Expert Review of Clinical Immunology
JF - Expert Review of Clinical Immunology
IS - 1
ER -