Clinical, immunological and molecular characteristics of 37 Iranian patients with X-linked agammaglobulinemia.
BACKGROUND
X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency characterized by an early onset of recurrent bacterial infections, a profound deficiency of all immunoglobulin isotypes and a markedly reduced number of peripheral B lymphocytes. Eighty-five percent of the patients with this phenotype have mutations in Bruton's tyrosine kinase (BTK) gene.


METHODS
To provide an informative outlook of clinical and immunological manifestations of XLA in Iran, 37 Iranian male patients with an age range of 1-34 years, followed over a period of 25 years, were studied. Twenty-four of the 37 patients were screened for BTK gene mutation using PCR-SSCP followed by direct sequencing. BTK protein expression assay was done by flow cytometry in 9 families.


RESULTS
All patients first presented with infectious diseases, the most common of which were respiratory tract infections. Eighteen different mutations were identified, 13 of which were novel: IVS1+5G>C, 1896G>A, 349delA, 1618C>T, 1783T>C, 2084A>G, 1346delT, 1351delGAG, 587A>G, IVS14-1G>A, IVS3+2T>C, 1482G>A, 1975C>A.


CONCLUSIONS
The fact that we found a great number of novel mutations in a relatively limited number of patients underlines the heterogeneity of BTK mutations in the Iranian population. The large number of new mutations indicates that extended studies in this region would be rewarding.
Aghamohammadi
Asghar
A
Division of Clinical Pediatric Immunology, Children's Medical Center, Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran. aghamohammadi@sina.tums.ac.ir
Fiorini
Maurilia
M
Moin
Mostafa
M
Parvaneh
Nima
N
Teimourian
Shahram
S
Yeganeh
Mehdi
M
Goffi
Francesca
F
Kanegane
Hirokazu
H
Amirzargar
Ali Akbar
AA
Pourpak
Zahra
Z
Rezaei
Nima
N
Salavati
Ali
A
Pouladi
Nima
N
Abdollahzade
Sina
S
Notarangelo
Luigi D
LD
Miyawaki
Toshio
T
Plebani
Alessandro
A
D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human