Alternative titles; symbols
ORPHA: 229717, 33110; DO: 0081135;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 22q11.23 | Agammaglobulinemia 2 | 613500 | Autosomal recessive | 3 | IGLL1 | 146770 |
A number sign (#) is used with this entry because of evidence that this form of autosomal recessive agammaglobulinemia, referred to here as agammaglobulinemia-2 (AGM2), is caused by homozygous or compound heterozygous mutation in the immunoglobulin lambda-like-1 gene (IGLL1; 146770) on chromosome 22q11.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal agammaglobulinemia, see AGM1 (601495).
Minegishi et al. (1998) reported a boy with agammaglobulinemia and markedly reduced numbers of B cells. He had onset of recurrent otitis at 2 months of age and was found to have hypogammaglobulinemia and absent B cells at 3 years of age when he developed Haemophilus meningitis complicated by arthritis. Laboratory studies at that time showed he was seronegative for the T cell-dependent antigens tetanus toxoid, diphtheria toxoid, and conjugated Haemophilus influenzae, despite previous immunization. He also failed to make antibody to the T cell-independent antigens in blood group substances. He had never had detectable CD19+ B cells by routine clinical testing. At 5 years of age, while receiving gammaglobulin replacement therapy, he had no measurable serum IgM and IgA. However, he had normal numbers of T cells and normal proliferative responses to mitogens.
The transmission pattern of AGM2 in the family reported by Minegishi et al. (1998) was consistent with autosomal recessive inheritance.
In a boy with agammaglobulinemia and markedly reduced numbers of B cells, Minegishi et al. (1998) identified compound heterozygosity for 2 mutations in the IGLL1 gene (146770.0001; 146770.0002). Each healthy parent was heterozygous for one of the mutations.
In 2 sisters (EGS539 and EGS540) with B-cell deficiency and increased susceptibility to bacterial infections, Moens et al. (2014) identified a homozygous 1-bp deletion (c.258delG; 146770.0003) in the IGLL1 gene. No additional clinical details were provided.
Minegishi, Y., Coustan-Smith, E., Wang, Y.-H., Cooper, M. D., Campana, D., Conley, M. E. Mutations in the human lambda-5/14.1 gene result in B cell deficiency and agammaglobulinemia. J. Exp. Med. 187: 71-77, 1998. [PubMed: 9419212] [Full Text: https://doi.org/10.1084/jem.187.1.71]
Moens, L. N., Falk-Sorqvist, E., Asplund, A. C., Bernatowska, E., Smith, C. I. E., Nilsson, M. Diagnostics of primary immunodeficiency diseases: a sequencing capture approach. PLoS One 9: e114901, 2014. Note: Electronic Article. [PubMed: 25502423] [Full Text: https://doi.org/10.1371/journal.pone.0114901]