Primary immunodeficiency complicated with Bacillus Calmette-Guerin infection: identification and clinical phenotype of a case of novel interleukin-12Rbeta1 gene mutation / 中华儿科杂志

ABSTRACT

<p><b>OBJECTIVE</b>Interleukin-12 receptor beta1 (IL-12 Rbeta1) deficiency is a rare primary immunodeficiency (PID) characterized by selective susceptibility to weakly virulent organisms, including Mycobacterium bovis, BCG, non-tuberculous environmental mycobacteria and non-typhoidal salmonellosis. The present study was conducted to identify the mutation type and to analyze clinical phenotype.</p><p><b>METHODS</b>Based on the typical clinical manifestations and immunologic tests in this case, a varieties of PIDs were excluded and IL-12Rbeta1 deficiency was suspected. IL-12Rbeta1 chain expressed on Epstein-Barr virus-transformed lymphoblastoid B cell lines were detected by flow cytometric assay. The IL-12Rbeta1 gene sequences of the patient and her parents were analyzed by PCR-directed sequencing. The IL-12Rbeta1 gene sequences of the patient's younger brother also had been analyzed prenatally and after birth.</p><p><b>RESULTS</b>After inoculating BCG, the patient suffered from multiple BCG infectious lymphadenitis. There was no detectable IL-12Rbeta1 on the Epstein-Barr virus-transformed lymphoblastoid B cell lines from the patient, while only mild expression on the cell line from her mother. Sequencing analysis by using sense and antisense primers separately, a novel IL-12Rbeta1 gene mutation was found in the patient which was homozygous single nucleotide substitution, a nonsense mutation with nucleotide substitution of C to T at position 853 (853C-->T) in exon 9 leading the glutamate at position 285 to the stop codon mutation (Q285X). The parents were carriers of the mutated IL-12Rbeta1 gene. But her younger brother has normal IL-12Rbeta1 gene.</p><p><b>CONCLUSION</b>The novel IL-12Rbeta1 gene mutation is responsible for BCG infection in this case and genetic analysis is useful in carrier detection and prenatal diagnosis is feasible when the mother had a baby with identified IL-12Rbeta1 gene mutation before.</p>