title: Mutations in genes underlying atypical familial mycobacteriosis are not found in tuberculosis patients from Siberian populations.
abstract: OBJECTIVE
  Atypical familial mycobacteriosis (AFM, OMIM #209950) is caused by mutations in genes regulating IL12/IFNG pathway. Some of the mutations exhibit incomplete penetrance, and they have been proposed to be involved in the common (polygenic) predisposition to tuberculosis (TB). We set out to test this hypothesis in two populations from Siberian region of Russia with high prevalence of TB.
  
  
  METHODS
  The prevalence of twelve mutations in IL12/IFNG pathway genes of were analysed in 331 Russians and 238 Tuvinians TB patients and in 279 healthy Russians and 265 healthy Tuvinians. A screening for new mutations and rare polymorphisms was carried out in 10 children with severe generalized TB and severe BCG-vaccine complications using Sanger's bidirectional sequencing.
  
  
  RESULTS
  Twelve mutations most commonly identified in AFM patients appeared to be "wild-type" monomorphic in the studied groups. No new mutations or rare polymorphisms were identified by sequencing. However, 15 common single nucleotide polymorphisms were found, none of which was associated with TB after correction for multiple testing.
  
  
  CONCLUSIONS
  The results of the study contradict with a hypothesis that mutations underlying AFM syndrome are involved in the predisposition to TB.
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia. Electronic address: aleksey.rudko@medgenetics.ru.
authors: Alexey A
authors: AA
authors: Rudko
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia.
authors: Anna F
authors: AF
authors: Garaeva
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia.
authors: Elena Yu
authors: EY
authors: Bragina
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia.
authors: Nadezda P
authors: NP
authors: Babushkina
authors: Siberian State Medical University, Tomsk, Russia.
authors: Olga V
authors: OV
authors: Kolokolova
authors: Siberian State Medical University, Tomsk, Russia.
authors: Olga N
authors: ON
authors: Lipaenkova
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia; Siberian State Medical University, Tomsk, Russia.
authors: Valery P
authors: VP
authors: Puzyrev
authors: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russia. Electronic address: mfreidin@medgenetics.ru.
authors: Maxim B
authors: MB
authors: Freidin
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017471:Receptors, Interferon / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics*; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D053762:Interleukin-12 Subunit p40; D017471:Receptors, Interferon; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C086185:IFNGR2 protein, human; C500879:IL12B protein, human; C508438:IL12RB1 protein, human; C494079:STAT1 protein, human
keywords: Atypical mycobacteriosis; Common susceptibility; Genetic polymorphism; Mendelian susceptibility; Tuberculosis