Familial pulmonary Mycobacterium avium complex disease

• Published in: American journal of respiratory and critical care medicine Vol. 161; no. 5; pp. 1643 - 1647
• Main Authors: Tanaka, E, Kimoto, T, Matsumoto, H, Tsuyuguchi, K, Suzuki, K, Nagai, S, Shimadzu, M, Ishibatake, H, Murayama, T, Amitani, R
• Format: Journal Article
• Language: English
• Published: United States 01-05-2000
• Subjects: Adult; Carrier Proteins - genetics; Cation Transport Proteins; DNA, Bacterial - analysis; DNA, Complementary - analysis; Family Health; Female; Genetic Predisposition to Disease; Humans; Immunity, Innate - genetics; Iron-Binding Proteins; Male; Membrane Proteins - genetics; Middle Aged; Mutation, Missense; Mycobacterium avium Complex - genetics; Mycobacterium avium-intracellulare Infection - immunology; Mycobacterium avium-intracellulare Infection - transmission; Polymorphism, Restriction Fragment Length; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - transmission
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.161.5.9907144

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.