Alternative titles; symbols
ORPHA: 229717, 33110; DO: 0081139;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q13.1 | ?Agammaglobulinemia 7, autosomal recessive | 615214 | Autosomal recessive | 3 | PIK3R1 | 171833 |
A number sign (#) is used with this entry because of evidence that autosomal recessive agammaglobulinemia-7 (AGM7) is caused by homozygous mutation in the PIK3R1 gene (171833) on chromosome 5q13. One such family has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal agammaglobulinemia, see AGM1 (601495).
De la Morena et al. (1995) reported a 6-month-old Hispanic girl of Chinese and Peruvian Indian ancestry who presented at age 3.5 months with interstitial pneumonia and gastroenteritis. Laboratory studies showed agammaglobulinemia, neutropenia, and lack of mature B cells in the peripheral blood and bone marrow. Lymph nodes showed lack of B cells, plasma cells, and germinal center formation. T cells and T-cell function were normal. Presence of CD10+ cells but absence of CD19+ cells and a 10-fold decrease of mature V-D-J-C-mu transcripts suggested a blockage at an earlier stage of B-cell development than that observed in the X-linked form of agammaglobulinemia (300755); genetic analysis excluded a defect in the BTK gene (300300).
Conley et al. (2012) provided follow-up of the patient reported by de la Morena et al. (1995), who was 19 years old and showed a severe defect in very early B-cell development. As a teenager, she developed erythema nodosum, juvenile idiopathic arthritis, and recurrent Campylobacter bacteremia and inflammatory bowel disease, suggesting disordered cytokine production. The family history was positive for 2 older brothers and 2 maternal uncles who died of acute infections between 9 and 18 months of age.
The transmission pattern of AGM7 in the family reported by Conley et al. (2012) was consistent with autosomal recessive inheritance.
In a patient with agammaglobulinemia-7, Conley et al. (2012) identified a homozygous truncating variant in the PIK3R1 (W298X; 171833.0001). The mutation, which was identified by exome sequencing, segregated with the disorder and was not found in 1,000 in-house control alleles. Screening of the PIK3R1 gene in 55 additional patients with defects in B-cell development did not identify any other mutations.
Conley, M. E., Dobbs, A. K., Quintana, A. M., Bosompem, A., Wang, Y.-D., Coustan-Smith, E., Smith, A. M., Perez, E. E., Murray, P. J. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85-alpha subunit of PI3K. J. Exp. Med. 209: 463-470, 2012. [PubMed: 22351933] [Full Text: https://doi.org/10.1084/jem.20112533]
de la Morena, M., Haire, R. N., Ohta, Y., Nelson, R. P., Litman, R. T., Day, N. K., Good, R. A., Litman, G. W. Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia. Europ. J. Immun. 25: 809-815, 1995. [PubMed: 7705412] [Full Text: https://doi.org/10.1002/eji.1830250327]