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Familial pulmonary Mycobacterium avium complex disease
E Tanaka1, T Kimoto, H Matsumoto
1Departments of Infectious Diseases and Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan.
Abstract:
We report two Japanese families affected by pulmonary Mycobacterium avium complex (MAC) disease, involving an older brother and younger sister in one family and two brothers in the second family. We investigated whether defects in the natural resistance-associated macrophage protein gene (NRAMP1) underlay susceptibility to MAC in these cases. All of the patients had computed tomographic findings of peripheral nodules and bronchiectasis. Pulse-field gel electrophoresis patterns of mycobacterial genomic DNA restriction fragments revealed that none of the MAC strains isolated from the patients was epidemiologically related to any of the others. Direct sequencing of the complementary DNA of the patients' NRAMP1 revealed a nonconservative missense mutation at codon 419 in one patient, which was heterozygous and was not seen in his affected sibling. No variations similar to those found in mice that show susceptibility to MAC were found. The results suggest an underlying genetic defect in host defense rather than exposure to an unusually virulent strain of MAC as the pathogenetic factor in MAC disease; however, alterations in the coding region of NRAMP1 do not appear to explain the susceptibility to MAC.
Insights
Genetic defects may predispose individuals to pulmonary Mycobacterium avium complex (MAC) disease. However, mutations in the NRAMP1 gene were not found to be the cause in these Japanese families.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Pulmonary Mycobacterium avium complex (MAC) disease can affect families.
- Investigating genetic factors for MAC susceptibility is crucial.
Observation:
- Two Japanese families with familial pulmonary MAC disease were studied.
- Patients presented with peripheral nodules and bronchiectasis on CT scans.
- MAC strains isolated were not epidemiologically related.
Findings:
- A nonconservative missense mutation in the NRAMP1 gene was identified in one patient, but it was heterozygous and not present in their affected sibling.
- No NRAMP1 variations similar to those in MAC-susceptible mice were found.
- The study suggests a genetic defect in host defense, but not in the NRAMP1 coding region, underlies MAC susceptibility.
Implications:
- The findings suggest a genetic basis for pulmonary MAC disease susceptibility.
- Alterations in the NRAMP1 gene coding region do not explain the observed susceptibility.
- Further research is needed to identify the specific genetic factors involved in MAC disease pathogenesis.