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X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations
Ist Teil von
Journal of clinical immunology, 2016-04, Vol.36 (3), p.187-194
Ort / Verlag
New York: Springer US
Erscheinungsjahr
2016
Quelle
SpringerLink
Beschreibungen/Notizen
Purpose
X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton’s tyrosine kinase (
BTK
) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton’s disease in 40 North African male patients.
Methods
Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2 % peripheral B cells were enrolled. The search for
BTK
gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing.
Results
We identified 33 different mutations in the
BTK
gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5 % vs 85 %). No strong evidence for genotype-phenotype correlation was observed.
Conclusions
This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.