A new case of autosomal recessive agammaglobulinaemia with impaired pre-B cell differentiation due to a large deletion of the IGH locus.
Males with X-linked agammaglobulinaemia (XLA) due to mutations in the Bruton tyrosine kinase gene constitute the major group of congenital hypogammaglobulinaemia with absence of peripheral B cells. In these cases, blockages between the pro-B and pre-B cell stage in the bone marrow are found. The remaining male and female cases clinically similar to XLA represent a genotypically heterogeneous group of diseases. In these patients, various autosomal recessive disorders have been identified such as mutations affecting IGHM, CD79A, IGLL1 genes involved in the composition of the pre-B cell receptor (pre-BCR) or the BLNK gene implicated in pre-BCR signal transduction. In this paper, we report on a young female patient characterised by a severe non-XLA agammaglobulinaemia that represents a new case of Igmu defect. We show that the B cell blockage at the pro-B to pre-B cell transition is due to a large homologous deletion in the IGH locus encompassing the IGHM gene leading to the inability to form a functional pre-BCR. The deletion extends from the beginning of the diversity (D) region to the IGHG2 gene, with all JH segments and IGHM, IGHD, IGHG3 and IGHG1 genes missing.


CONCLUSIONS
alteration in Igmu expression seems to be relatively frequent and could account for most of the reported cases of autosomal recessive agammaglobulinaemia.
Milili
Michèle
M
Centre d'Immunologie de Marseille-Luminy, case 906, 13288 Marseille cedex 09, France.
Antunes
Henedina
H
Blanco-Betancourt
Carla
C
Nogueiras
Ana
A
Santos
Eugénia
E
Vasconcelos
Júlia
J
Castro e Melo
João
J
Schiff
Claudine
C
D000361:Agammaglobulinemia / Q000097:blood / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D002675:Child, Preschool; D002872:Chromosome Deletion; D017931:DNA Primers; D005260:Female; D005803:Genes, Immunoglobulin; D005808:Genes, Recessive; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D010641:Phenotype; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell