Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia.
BACKGROUND
X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial.


METHODS
We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis.


RESULTS
Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections.


CONCLUSIONS
A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.
Lee
Pamela P W
PP
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.
Chen
Tong-Xin
TX
Jiang
Li-Ping
LP
Chan
Koon-Wing
KW
Yang
Wanling
W
Lee
Bee-Wah
BW
Chiang
Wen-Chin
WC
Chen
Xiang-Yuan
XY
Fok
Susanna F S
SF
Lee
Tsz-Leung
TL
Ho
Marco H K
MH
Yang
Xi-Qiang
XQ
Lau
Yu-Lung
YL
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007239:Infections / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human