title: Genetic basis of patients with bacille Calmette-Guérin osteomyelitis in Japan: identification of dominant partial interferon-gamma receptor 1 deficiency as a predominant type.
abstract: Interferon (IFN)-gamma-mediated immunity plays an important role in host defense against intracellular pathogens, especially mycobacteria. Six Japanese children with bacille Calmette-Guérin (BCG) osteomyelitis were evaluated (1 disseminated, 3 multiple, and 2 solitary types) for mutations of genes involved in interleukin-12-dependent, IFN-gamma-mediated immunity. Heterozygous small deletions with frameshift (818del4 and 811del4) that are consistent with the diagnosis of partial dominant IFN-gamma receptor 1 (IFN-gammaR1) deficiency were detected in 3 unrelated patients. Expression of IFN-gammaR1 on monocytes was significantly increased in all 3 patients. Screening of family members with recurrent and disseminated mycobacterial infections found the identical deletion in 1 of the fathers. Antimycobacterial treatment was effective in these patients and resulted in good clinical outcome. This study demonstrated that partial dominant IFN-gammaR1 deficiency was the most common in Japanese patients who showed predisposition to curable BCG osteomyelitis.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. yuka@pediatr.med.kyushu-u.ac.jp
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nomura
authors.forename: Koichi
authors.initials: K
authors.lastname: Kusuhara
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.forename: Saifuddin
authors.initials: S
authors.lastname: Ahmed
authors.forename: Kaoru
authors.initials: K
authors.lastname: Obinata
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hamada
authors.forename: Yuri
authors.initials: Y
authors.lastname: Okimoto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D007564:Japan; D008297:Male; D009154:Mutation; D009164:Mycobacterium Infections / Q000382:microbiology; D010019:Osteomyelitis / Q000209:etiology* / Q000235:genetics*; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D001500:BCG Vaccine; D017471:Receptors, Interferon; D018664:Interleukin-12; D007371:Interferon-gamma