Different Penetrance Of Disseminated Infections Caused By Nontuberculous Mycobacteria In Mendelian Susceptibility To Mycobacterial Disease Associated With A Novel Mutation

Giménez-Sánchez, Francisco; Cobos‐Carrascosa, Elena; Sánchez-Forte, Miguel; Martínez-Lirola, Miguel; López-Ruzafa, Encarnación; Galera-Martinez, Rafael; Rabes, T. del Rosal; Martínez‐Gallo, Mónica

doi:10.1097/inf.0000000000000099

Cited by 7 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MSMD is a rare inherited condition characterized by predisposition to recurrent and/or disseminated infections caused by weakly virulent mycobacteria as BCG vaccine. 1,2 Mycobacterial infection usually begins in childhood, rarely later during adolescence and adulthood. Clinical spectrum is very wide, ranging from localized to disseminated infections with one or more mycobacterial species.…”

Section: Discussionmentioning

confidence: 99%

Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency

et al. 2017

View full text Add to dashboard Cite

Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity. We report here a case of multifocal Bacillus Calmette-Guérin osteomyelitis in a context Mendelian susceptibility to mycobacterial disease mimicking a metastatic neuroblastoma in a child presenting with delayed growth. The investigation of her twin sister showed the same disease. A heterozygous mutation in exon 22 of STAT1 gene was found in both sisters, another sister and the father being healthy and heterozygous for the same mutation.

show abstract

Section: Discussionmentioning

confidence: 99%

Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Indeed, 47 of the 179 patients died (26%), 8 are asymptomatic (the oldest being 22 years old in 2010) and 124 were alive at the time of their description, the oldest of these patients being 51 years old in 2010 [28, 198]. Mycobacterial infections are the most frequent infections observed in these patients (BCG, M. avium , M. avium intracellulare complex, M. chelonae , M. fortuitum , M. fortuitum - chelonae complex, M. genevense , M. gordonae , M. tilburgii , M. triplex , M. simiae ) [28, 34, 36, 86, 116, 190, 193, 194, 198, 199, 204, 206, 208–210, 214, 215, 235, 236]. Remarkably, BCG vaccination or disease protects against subsequent EM disease [28, 194] (Figure 5).…”

Section: Complete Il-12rβ1 Deficiencymentioning

confidence: 99%

“…Six patients with AR complete IL-12Rβ1 deficiency presented with TB as their sole infectious phenotype, probably in the course of primary infection, providing proof-of-principle for the monogenic determinism of severe TB [20, 21, 24, 25, 83]. Interestingly, more than a third of all AR complete IL-12Rβ1-deficient patients (69 of 179 patients (38%)) have developed invasive salmonellosis [28, 30, 31, 39, 43, 188, 190, 196, 202, 206, 207, 233], associated with leukocytoclastic vasculitis in some cases [28, 196, 202]. Klebsiella pneumoniae is also pathogenic in patients with this deficiency [28, 31, 34, 38].…”

Section: Complete Il-12rβ1 Deficiencymentioning

confidence: 99%

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Bustamante

Boisson–Dupuis

Abel

et al. 2014

Seminars in Immunology

594

655

View full text Add to dashboard Cite

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity.

show abstract

“…Warts/HPV infections [51] Mycobacterial infections [68][69][70] Congenital lymphedema [71-73, 75, 76] Pulmonary alveolar proteinosis [77] TERT/TERC CEBPA RUNX1 tests and has not demonstrated any systemic infections or signs of MDS/AML although cognitive development appears to be delayed.…”

Section: Mds/aml [67]mentioning

confidence: 99%

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

et al. 2015

View full text Add to dashboard Cite

Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature.

show abstract

Different Penetrance Of Disseminated Infections Caused By Nontuberculous Mycobacteria In Mendelian Susceptibility To Mycobacterial Disease Associated With A Novel Mutation

Cited by 7 publications

References 10 publications

Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency

Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

Contact Info

Product

Resources

About