Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia

S. Ferrari, R. Zuntini, V. Lougaris, A. Soresina, V. Šourková, M. Fiorini, S. Martino, P. Rossi, M. C. Pietrogrande, B. Martire, G. Spadaro, F. Cardinale, F. Cossu, P. Pierani, I. Quinti, C. Rossi, A. Plebani

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the μ heavy chain (μHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G>A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the μHC and in the λ5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.

Original languageEnglish
Pages (from-to)325-333
Number of pages9
JournalGenes and Immunity
Volume8
Issue number4
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Genes
Mutation
B-Lymphocytes
Agammaglobulinemia
RNA Splice Sites
Immunoglobulin Isotypes
Genetic Association Studies
Single Nucleotide Polymorphism
non-Bruton type Agammaglobulinemia
Nucleotides
Bone Marrow
Infection
Bruton type agammaglobulinemia
Agammaglobulinaemia tyrosine kinase

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Ferrari, S., Zuntini, R., Lougaris, V., Soresina, A., Šourková, V., Fiorini, M., ... Plebani, A. (2007). Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. Genes and Immunity, 8(4), 325-333. https://doi.org/10.1038/sj.gene.6364391

Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. / Ferrari, S.; Zuntini, R.; Lougaris, V.; Soresina, A.; Šourková, V.; Fiorini, M.; Martino, S.; Rossi, P.; Pietrogrande, M. C.; Martire, B.; Spadaro, G.; Cardinale, F.; Cossu, F.; Pierani, P.; Quinti, I.; Rossi, C.; Plebani, A.

In: Genes and Immunity, Vol. 8, No. 4, 06.2007, p. 325-333.

Research output: Contribution to journalArticle

Ferrari, S, Zuntini, R, Lougaris, V, Soresina, A, Šourková, V, Fiorini, M, Martino, S, Rossi, P, Pietrogrande, MC, Martire, B, Spadaro, G, Cardinale, F, Cossu, F, Pierani, P, Quinti, I, Rossi, C & Plebani, A 2007, 'Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia', Genes and Immunity, vol. 8, no. 4, pp. 325-333. https://doi.org/10.1038/sj.gene.6364391
Ferrari, S. ; Zuntini, R. ; Lougaris, V. ; Soresina, A. ; Šourková, V. ; Fiorini, M. ; Martino, S. ; Rossi, P. ; Pietrogrande, M. C. ; Martire, B. ; Spadaro, G. ; Cardinale, F. ; Cossu, F. ; Pierani, P. ; Quinti, I. ; Rossi, C. ; Plebani, A. / Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. In: Genes and Immunity. 2007 ; Vol. 8, No. 4. pp. 325-333.
@article{ff2bbcc13b304f0f90bfc8778b57b69c,
title = "Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia",
abstract = "Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the μ heavy chain (μHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G>A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the μHC and in the λ5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.",
author = "S. Ferrari and R. Zuntini and V. Lougaris and A. Soresina and V. Šourkov{\'a} and M. Fiorini and S. Martino and P. Rossi and Pietrogrande, {M. C.} and B. Martire and G. Spadaro and F. Cardinale and F. Cossu and P. Pierani and I. Quinti and C. Rossi and A. Plebani",
year = "2007",
month = "6",
doi = "10.1038/sj.gene.6364391",
language = "English",
volume = "8",
pages = "325--333",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia

AU - Ferrari, S.

AU - Zuntini, R.

AU - Lougaris, V.

AU - Soresina, A.

AU - Šourková, V.

AU - Fiorini, M.

AU - Martino, S.

AU - Rossi, P.

AU - Pietrogrande, M. C.

AU - Martire, B.

AU - Spadaro, G.

AU - Cardinale, F.

AU - Cossu, F.

AU - Pierani, P.

AU - Quinti, I.

AU - Rossi, C.

AU - Plebani, A.

PY - 2007/6

Y1 - 2007/6

N2 - Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the μ heavy chain (μHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G>A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the μHC and in the λ5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.

AB - Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the μ heavy chain (μHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G>A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the μHC and in the λ5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.

UR - http://www.scopus.com/inward/record.url?scp=34250006519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250006519&partnerID=8YFLogxK

U2 - 10.1038/sj.gene.6364391

DO - 10.1038/sj.gene.6364391

M3 - Article

VL - 8

SP - 325

EP - 333

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 4

ER -