Agammaglobulinemia is a primary immunodeficiency disorder characterized by profoundly low or absent serum antibodies and low or absent circulating B cells. The most common form is X-linked agammaglobulinemia (XLA) caused by mutations in BTK gene. The remaining cases, clinically similar to XLA, are autosomal recessive agammaglobulinemia (ARA). Nearly 30% of ARA cases present mutations in the μ heavy constant region gene IGHM. Here, we present a 7-month-old patient, born from non-consanguineous parents, who is affected by ARA due to defect in the μ heavy chain. The genetic study showed that the patient is compound heterozygous for an IGHM gene deletion and the novel nonsense mutation X57331.1:g.275C>A (p.Tyr43*) (ClinVar Accession Number: SCV000537868.1). This finding allows for an adequate genetic counseling to the family and also broadens the spectrum of already described point mutations at this locus. The IGHM gene is very complex and it is likely that yet unidentified mutations appear in other patients.
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Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol 2009; 27: 199–227.
Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM et al. Mutations in the mu heavy chain gene in patients with agammaglobulinemia. N Engl J Med 1996; 335: 1486–1493.
Schiff C, Lemmers B, Deville A, Fougereau M, Meffre E . Autosomal primary immunodeficiencies affecting human BM B-cell differentiation. Immunol Rev 2000; 178: 91–98.
López Granados E, Porpiglia AS, Hogan MB, Matamoros N, Krasovec S, Pignata C et al. Clinical and molecular analysis of patients with defects in mu heavy chain gene. J Clin Invest 2002; 110: 1029–1035.
Milili M, Antunes H, Blanco-Betancourt C, Nogueiras A, Santos E, Vasconcelos J et al. A new case of autosomal recessive agammaglobulinemia with impaired pre-B cell differentiation due to a large deletion of the IGH locus. Eur J Pediatr 2002; 161: 479–484.
Ferrari S, Zuntini R, Lougaris V, Soresina A, Sourková V, Fiorini M et al. Molecular analysis of the pre-B complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. Genes Imun 2007; 8: 325–333.
Mohammadzadeh I, Yeganeh M, Aghamohammadi A, Parvaneh N, Behniafard N, Abolhassani H et al. Severe primary antibody deficiency due to a novel mutation of μ heavy chain. J Investig Allergol Clin Immunol 2012; 22: 63–79.
van Zelm M, Geertsema C, Nieuwenhuis N, de Ridder D, Conley ME, Schiff C et al. Gross deletions involving IGHM, BTK, or Artemis: a Model for genomic lesions mediated by transposable elements. Am J Hum Genet 2008; 82: 320–322.
Meffre E, Milili M, Blanco-Betancourt C, Antunes H, Nussenzweig MC, Schiff C . Inmunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development. J Clin Invest 2001; 108: 879–886.
We would like to thank the patient's parents for their cooperation in this study.
The authors declare no conflict of interest.
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Silva, P., Justicia, A., Regueiro, A. et al. Autosomal recessive agammaglobulinemia due to defect in μ heavy chain caused by a novel mutation in the IGHM gene. Genes Immun 18, 197–199 (2017). https://doi.org/10.1038/gene.2017.14
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