A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases

Ueki, Minoru; Yamada, Masafumi; Ito, Kenta; Tozawa, Yusuke; Morino, Saeko; Horikoshi, Yuho; Takada, Hidetoshi; Abdrabou, Shimaa Said Mohamed Ali; Takezaki, Shunichiro; Kobayashi, Ichiro; Ariga, Tadashi

doi:10.1016/j.clim.2016.11.004

Cited by 19 publications

(15 citation statements)

References 23 publications

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“…Since the discovery of its first genetic etiology in 1996, MSMD has been reported and a causal genetic lesion described in 501 individuals from 356 kindreds originating from 57 countries on five continents (Figure a). Over this period, the genetic dissection of MSMD in these patients has revealed this condition to be caused by inborn errors of interferon (IFN)‐γ immunity . These findings confirm that IFN‐γ, first described in 1965 as an antiviral IFN, is actually the macrophage‐activating factor, as shown in 1983 .…”

Section: Introductionsupporting

confidence: 61%

“…Since the last comprehensive review on MSMD in 2014, three new genetic disorders have been reported, caused by mutations of TYK2 and SPPL2A, (two novel genetic etiologies) and IFNGR2 (a novel allelic form). Moreover, new mutations associated with the other 18 disorders have also been reported . We also discuss here two recently reported syndromic forms of MSMD: AR RORγ/RORγT and Janus kinase (JAK)1 deficiencies .…”

Section: Introductionmentioning

confidence: 80%

“…Since 2014, 34 new disease‐causing mutations have been reported at six MSMD loci already discovered before this date, including IFNGR1, IFNGR2 , IL12RB1 , IL12B , STAT1 and NEMO . Interestingly, the two new hypomorphic NEMO mutations underlie mycobacterial diseases without anhidrotic ectodermal dysplasia .…”

Section: New Mutations At Known Msmd Locimentioning

confidence: 99%

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Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-c immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (1) a new genetic etiology, autosomal recessive signal peptide peptidase-like 2 A deficiency, (2) TYK2-deficient patients with a clinical phenotype of MSMD, (3) an allelic form of partial recessive IFN-cR2 deficiency, and (4) two forms of syndromic MSMD: RORc/RORcT and JAK1 deficiencies. These recent findings illustrate how genetic and immunological studies of MSMD can shed a unique light onto the mechanisms of protective immunity to mycobacteria in humans.

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Section: Introductionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 80%

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Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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“…Moreover, new mutations associated with the other 18 disorders have also been reported. [5][6][7]10,12,18,22,25,30,32,34,36,42,43,[45][46][47][48][49]57 We also discuss here two recently reported syndromic forms of MSMD: AR RORγ/RORγT and JAK1 deficiencies. 58,59 Like three previously reported etiologies of syndromic MSMD, AR STAT1 and IRF8 deficiencies, 1 and AD GATA2 deficiency, 60 RORγ/RORγT and JAK1 deficiencies underlie mycobacterial diseases in the context of other infections.…”

Section: Introductionmentioning

confidence: 92%

“…Since 2014, 1 34 new disease-causing mutations have been reported at six MSMD loci already discovered before this date, including IFNGR1, 10,40,42,43,45,46,48,49 IFNGR2, 5,10,47 IL12RB1, 6,12,22,25,30 IL12B, 7 STAT1, [32][33][34] and NEMO. 18,[36][37][38] Interestingly, the two new hypomorphic NEMO mutations underlie mycobacterial diseases without anhidrotic ectodermal dysplasia (EDA).…”

Section: New Mutations At Known Msmd Locimentioning

confidence: 99%

Faculty Opinions recommendation of Mendelian susceptibility to mycobacterial disease: 2014-2018 update.

Lionakis

2020

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (i) a new genetic etiology, autosomal recessive SPPL2a deficiency, (ii) TYK2-deficient patients with a clinical phenotype of MSMD, (iii) an allelic form of partial recessive IFN-γR2 deficiency, and (iv) two forms of syndromic MSMD: RORγ/RORγT and JAK1 deficiencies. These recent findings illustrate how genetic and immunological studies of MSMD can shed a unique light onto the mechanisms of protective immunity to mycobacteria in humans.

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Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12Rβ1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

et al. 2018

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Purpose. Inborn errors of IFN-γ-mediated immunity underlie Mendelian Susceptibility to Mycobacterial Disease (MSMD), which is characterized by an increased susceptibility to severe and recurrent infections caused by weakly virulent mycobacteria, such as Bacillus Calmette–Guérin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM). Methods. In this study, we investigated four patients from four unrelated consanguineous families from Isfahan, Iran with disseminated BCG disease. We evaluated the patients’ whole blood cell response to IL-12 and IFN-γ, IL-12Rβ1 expression on T-cell blasts, and sequenced candidate genes. Results. We reported four patients from Isfahan, Iran, ranging from 3 months to 26 years old, who had impaired IL-12 signaling. All patients suffered from BCG infectious diseases. One of them presented mycobacterial osteomyelitis as a form of infection. By Sanger sequencing, we identified three different types of homozygous mutations in IL12RB1. Expression of IL-12Rβ1 was completely abolished in the four patients with IL12RB1 mutations. Conclusions. IL-12Rβ1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321X mutant IL-12Rβ1 protein. Mycobacterial osteomyelitis is another type of location of mycobacterial infection in an IL-12Rβ1-deficient patient, notified for the first time in this study.

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A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases

Cited by 19 publications

References 23 publications

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

Faculty Opinions recommendation of Mendelian susceptibility to mycobacterial disease: 2014-2018 update.

Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12Rβ1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

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