Immunodeficiency 13

A number sign (#) is used with this entry because of evidence that immunodeficiency-13 (IMD13) is caused by heterozygous mutation in the UNC119 gene (604011) on chromosome 17q11. One such family has been reported.

Description

Idiopathic CD4 lymphopenia (ICL) is a rare and heterogeneous syndrome defined by a reproducible reduction in the CD4 T-lymphocyte count (less than 300 cells per microliter or less than 20% of total T cells) in the absence of HIV infection or other known causes of immunodeficiency. ICL predisposes to infections and malignancy (summary by Gorska and Alam, 2012).

Clinical Features

Gorska and Alam (2012) studied a 32-year-old woman who had a history of recurrent sinusitis, otitis media, and shingles; persistent severe fungal infections of fingernails and toenails with partial loss of nails; fungal dermatitis; 2 episodes of bacterial pneumonia followed by bronchiolitis obliterans organizing pneumonia; and oral herpetic lesions. She had reduced CD4 cell counts of less than 300 cells per microliter on multiple evaluations, as well as lymphopenia and low CD3 T-cell counts. Her levels of IgM, IgA, and IgG and its subclasses were normal, and she had an unimpaired response to bacterial antigens. Her neutrophil count and function were normal. T-cell receptor (TCR; see 186880) stimulation triggered only a marginal increase in LCK (153390) activity in patient CD4 T cells.

Molecular Genetics

In a 32-year-old woman, 1 of 3 patients with CD4 lymphopenia in whom known causes had been excluded, Gorska and Alam (2012) identified a missense mutation in the UNC119 gene (G22V; 604011.0002). To confirm that the reduction in LCK activity observed in the latter patient was not due to a defect in the LCK gene, Gorska and Alam (2012) also sequenced LCK but found no mutations. No UNC119 mutations were found in 8 patients with secondary CD4 lymphopenia or in 60 controls.