Bare Lymphocyte Syndrome, Type I

A number sign (#) is used with this entry because bare lymphocyte syndrome type I can be caused by mutation in the TAP2 (170261), TAP1 (170260), or TAPBP (601962) gene.

Clinical Features

In the review by de la Salle et al. (1999), only 9 well-documented cases of HLA class I deficiency with normal expression of class II molecules were found. Contrary to type II (209920) and type III bare lymphocyte syndromes, which are characterized by the early onset of severe combined immunodeficiency, class I antigen deficiencies are not accompanied by particular pathologic manifestations during the first years of life, although chronic lung disease develops in late childhood. Also in contrast to type II or type III BLS, pathology of the gut (diarrhea) is not observed. Systemic infections have not been described in HLA class I-deficient patients. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract and extend from the upper to the lower airway. Bronchiectasis, emphysema, panbronchiolitis, and bronchial obstruction have been described. De la Salle et al. (1999) noted a high frequency of nasal polyps and involvement of the nasal sinuses.

Moins-Teisserenc et al. (1999) described 5 patients with a syndrome of chronic necrotizing granulomatous lesions, small-vessel vasculitis, recurrent respiratory-tract infections, and development of bronchiectasis. A diagnosis of granulomatosis with polyangiitis (608710) was considered but abandoned because of an incompatible disease course and resistance of immunosuppressant treatments. All 5 patients had a severe decrease in cell surface expression of HLA class I molecules and defective expression of the TAP complex. Autoreactive natural killer (NK) cells and gamma/delta T lymphocytes were found in the peripheral blood of 2 patients.

Molecular Genetics

In a family in Morocco with type I BLS, de la Salle et al. (1994) identified a mutation in the TAP2 gene (see 170261.0004).

In patients with type I BLS with granulomatous changes, Moins-Teisserenc et al. (1999) identified a homozygous mutation in the TAP2 gene (170261.0005).

In a 46-year-old Japanese woman originally reported by Maeda et al. (1985) with type I bare lymphocyte syndrome, Furukawa et al. (1999) identified homozygosity for a splice site mutation in intron 1 of the TAP1 gene (170260.0004). Both TAP1 and TAP2 proteins were undetectable in the patient's B-cells, but sequencing of TAP2 revealed no mutations. The patient had sinusitis, chronic bronchitis, and a punched-out ulcer on her left pretibial region. Her first-cousin parents and other family members were heterozygous for the mutation in TAP1.

In a patient with tapasin deficiency and type I BLS, Yabe et al. (2002) identified a mutation in the TAPBP gene (see 601962.0001).