Three novel compound heterozygous IL12RB1 mutations in Chinese patients with Mendelian susceptibility to mycobacterial disease

Zhou, Xiaopei; Jia, Weimin; Ni, Zhengyi; Wang, Ali; Liu, Zhenxing; Hou, Meiqi; Zhou, Mi; Tang, Zhongwen; Zhang, Dazhi; Li, Lei; Han, Tiantian; Tan, Yang; Luo, Geng; Wang, Jiarui; Wu, Yanling; Zhang, Xianqin

doi:10.1371/journal.pone.0215648

Cited by 8 publications

(7 citation statements)

References 13 publications

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“…1 ). All variants have been previously reported [ 21 , 22 ] except for c.1750C > T, a missense variant that is exceedingly rare (gnomAD exomes AF 0.000004, allele count one Latino individual) and likely pathogenic, with a CADD Phred score of 23.4 (minimum significance cutoff value for IL12RB1 at 95% CI 3.65) [ 23 ], classified as Pathogenic in ClinVar, and as VUS by ACMG criteria ( http://varsome.com .) (Supplementary Figs.…”

Section: Resultsmentioning

confidence: 99%

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

Lara¹,

Nakashimada²,

León-Lara³

et al. 2022

J Clin Immunol

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Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis -Bacillus Calmette–Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella , as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 ( n = 13), IFNGR1 ( n = 3), and IFNGR2 ( n = 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-022-01357-8.

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Section: Resultsmentioning

confidence: 99%

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

Lara¹,

Nakashimada²,

León-Lara³

et al. 2022

J Clin Immunol

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“…Globally, a wide range of clinical manifestations of MSMD, from transient localized to persistent disseminated infections with impaired granuloma formation, has been reported, and Salmonella infections occurred in about half the reported patients (43). In China, 65 patients with MSMD in 20 publications (35,(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72) were described, along with 9 gene mutations (IFNGR1, IFNGR2, ISG15, IL12B, IL12RB1, STAT1, TYK2, NEMO, CYBB) were noted. IL-12RB1 deficiency was the most common molecular defect, accounting for 52% of all cases, followed by IFNGR1 (22%) and STAT1 (9%) (Figure 2).…”

Section: Genetic Profiles and Clinical Manifestations Of Reported Msm...mentioning

confidence: 99%

“…The other 35 Chinese cases were reported in 19 publications from Mainland China, Hongkong, and Taiwan (35,(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72). Of them, 19 (54.3%) were female and 16 (45.7%) were male; the medium age at onset was 4 months.…”

Section: Genetic Profiles and Clinical Manifestations Of Reported Msm...mentioning

confidence: 99%

“…Lee PP et al ( 63 ) reported two patients, one suffered BCGosis with a novel nonsense mutation 853C>T (Q285X) in exon 9, and another one suffered BCGitis with a mutation 1791 + 2T>G. The heterozygous mutation of the second patient has also been discovered in two other Chinese patients ( 66 , 67 ). Zhou XP et al ( 68 ) identified three novel compound heterozygous mutations in the IL12RB1 gene (c.635G>A, c.765delG; c.632G>C, c.847C>T; c.64G>A, c.1673insGAGCTTCCTGAG) in three Chinese families with MSMD. One of the heterozygous mutations, c.632G > C, has been discovered in a Chinese patient from Taiwan who carried the homozygous mutation.…”

Section: Genetic Profiles and Clinical Manifestations Of Reported Msm...mentioning

confidence: 99%

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An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China

et al. 2022

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Mendelian susceptibility to mycobacterial disease (MSMD) arises from a group of rare inherited errors of immunity that result in selective susceptibility of otherwise healthy people to clinical disease caused by low virulence strains of mycobacteria, such as Mycobacterium bovis Bacille Calmette-Guérin (BCG) and environmental mycobacteria. Patients have normal resistance to other pathogens and no overt abnormalities in routine immunological and hematological evaluations for primary immunodeficiencies. At least 19 genes and 34 clinical phenotypes have been identified in MSMD. However, there have been no systematic reports on the clinical characteristics and genetic backgrounds of MSMD in China. In this review, on the one hand, we summarize an update findings on molecular defects and immunological mechanisms in the field of MSMD research globally. On the other hand, we undertook a systematic review of PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, CNKI, and Wanfang to identify articles published before Jan 23, 2022, to summarize the clinical characteristics, diagnosis, treatment, and prognosis of MSMD in China. All the English and Chinese publications were searched without any restriction on article types.

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“…IL-12Rβ1 is responsible for the formation of IL-12 and IL-23 receptors. It has been reported that IFN-γ production is low and there is no IL-12 response (T and NK cells) in patients with IL-12Rβ1 deficiency (6,7).…”

Section: Introductionmentioning

confidence: 99%

Genetic and Clinical Profiling of Mendelian Susceptibility to Mycobacterial Disease Patients; Single Center Experience

Nepesov¹,

Fırtına²,

Aygün³

et al. 2022

jarhs

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This work is licensed under Creative Commons Attribution-NonCommercial 4.0 International License ÖZ Amaç: Mikobakteriyel hastalığa (MSMD) Mendel duyarlılığı, Bacille Calmette-Guérin (BCG) aşısı veya tüberküloz dışı mikobakteriyel enfeksiyonlarla gelişen primer immün yetmezliklerin bir alt grubudur. Klinik semptomlar, lokalize enfeksiyondan yayılmış enfeksiyona kadar geniş bir spektruma sahiptir. Gereç ve Yöntem: Bu çalışmada; MSMD fenotipli 13 hastada tüm ekzom dizileme (WES) yaptık. Tüm varyantlar Sanger dizileme ile doğrulandı. Bizim kohortumuzda ortalama yaş 8.41 yıl (en az 3 -en fazla 14 yıl) ve ortalama semptom başlangıç yaşı 4.6 idi. Bulgular: Dokuz hastada; IFNGR1 (n=2), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1) ve CYBB (n=1) gen varyantları bulduk. Hastalarımızda en çok lenfadenit (%61,5), osteomiyelit (%38) ve miliyer tüberküloz (%31) mevcuttu. Biri hariç tüm hastalara BCG aşısı yapıldı. İki hastada aşılamadan sonra BCGitis gelişti. Üç hasta, yayılmış BCG enfeksiyonundan (BCGosis) muzdaripti. Sonuç: Bulgularımız, enfeksiyon hastalıklarının genetik temelinin anlaşılmasında ve tedavi seçeneklerine karar verilmesinde bir yaklaşım olarak ağır enfeksiyonlu hastalarda moleküler tanının önemini göstermektedir. IFN aracılı bağışıklık genlerinin eksikliği, MSMD'nin patogenezinde çok önemli bir rol oynar ve BCGitis'li pediatrik hastalarda düşünülmelidir.

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Three novel compound heterozygous IL12RB1 mutations in Chinese patients with Mendelian susceptibility to mycobacterial disease

Cited by 8 publications

References 13 publications

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China

Genetic and Clinical Profiling of Mendelian Susceptibility to Mycobacterial Disease Patients; Single Center Experience

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