Somatic NOD2 mosaicism in Blau syndrome

Arocena, Jaime de Inocencio; Mensa‐Vilaró, Anna; Tejada-Palacios, P.; Enriquez-Merayo, Eugenia; González‐Roca, Eva; Magri, Giuliana; Ruiz-Ortiz, Estíbaliz; Cerutti, Andrea; Yagüe, Jordi; Aróstegui, Juan I.

doi:10.1016/j.jaci.2014.12.1941

Cited by 63 publications

(32 citation statements)

References 9 publications

(15 reference statements)

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“…The determination of the degree of gonadal mosaicism would indicate the level of variant distribution in the body, and could also establish transmission risk to offspring, unlike germline mutations where there is a 50% chance of transmitting the mutated allele; although this study was unable to derive this figure. The conclusion that there are milder phenotypes on the BS spectrum associated with de novo mutations than those phenotypes seen in patients with BS with germline mutations is a concept that has also been seen in other SAID, such as CAPS54 63 and TRAPS,59 as well as one BS case itself 60. With this particular case, the presence of a somatic NOD2 mutation in the patient's haematopoietic cells is likely to be the cause of the main symptoms of an inflammatory nature.…”

Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 80%

“…With this particular case, the presence of a somatic NOD2 mutation in the patient's haematopoietic cells is likely to be the cause of the main symptoms of an inflammatory nature. However, the later disease onset and a ‘relatively benign course’, with decreased joint involvement, in the 2015 study,60 as compared with other germline cases is indicative of a wider range of clinical phenotypes, although very dependent on the level of mosaicism.…”

Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 91%

“…The initial account of somatic mosaicism in Blau syndrome (BS) was first reported by de Inocencio et al 60 in 2015. Targeted deep sequencing of both haematological and non-haematological-derived DNA ascertained the presence of the p.Arg334Gln NOD2 mutation, first suspected during Sanger chromatogram analysis of a ‘subtle’ adenine peak at C.1001 as compared with a decrease in the WT.…”

Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 99%

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Autoinflammatory diseases: update on classification diagnosis and management

2016

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The spectrum of systemic autoinflammatory disorders broadens continually. In part, this is due to the more widespread application of massive parallel sequencing, helping with novel gene discovery in this and other areas of rare diseases. Some of the conditions that have been described fit neatly into a conventional idea of autoinflammation. Others, such as Interferon-mediated autoinflammatory diseases, are broadening the concept which we consider to be autoinflammatory disorders. There is also a widening of the clinical phenotypes associated with certain genetic mutations, as genetic testing is used more regularly and increasing numbers of patients are screened. It is also increasingly evident that both autoinflammatory and autoimmune problems are frequently seen as complications of primary immunodeficiency disorders.The aim of this review is to provide an update on some recently discovered conditions, and to discuss how these disorders help to define the concept of autoinflammation. The review will also cover recent discoveries in the biology of innate-immune mediated inflammation, and describe how this has provided the biological rationale for using anti-IL-1 therapies in the treatment of many such conditions. Finally, we discuss the importance of recognising somatic mutations as causes of autoinflammatory clinical phenotypes, and provide practical advice on how this could be tackled in everyday clinical practice.

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Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 80%

Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 91%

Section: Saids Of Unknown Aetiology and Somatic Mosaicism/mutationsmentioning

confidence: 99%

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Autoinflammatory diseases: update on classification diagnosis and management

2016

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“…Another consideration is the occurrence of somatic mosaicism: after careful visual inspection of nucleotide-binding oligomerization domain protein 2 (NOD2) sequencing data in a patient with Blau Syndrome, a known pathological variant was found in hematological and non-hematological samples at allele frequency of 5-11%. 50 Somatic mosaicism was also reported in two patients with Schnitzler syndrome, characterized by chronic urticaria, monoclonal gammopathy and inflammation, with pathogenic gene mutations in NLRP3 , a gene involved in cryopyrin periodic syndrome (CAPS), restricted to the myeloid lineage. 51 …”

Section: Diagnostic Testing Of Primary Immunodeficienciesmentioning

confidence: 99%

Advances in clinical immunology in 2015

Chinen

Notarangelo

Shearer

2016

Journal of Allergy and Clinical Immunology

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Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immune deficiencies (PIDs) to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by mutations found in one gene, such as a specific RTEL1 mutation causing isolated NK cell deficiency, and mutations in RAB27 resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole exome sequencing to identify gene defects, and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several PIDs, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy.

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“…Moreover, even though SAIDs are characterised by early onset, adult patients carrying low penetrant mutations have also been described for cryoyrin-associated periodic syndrome (CAPS), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF),21–24 thus indicating genetic and clinical complexity. Finally, somatic mosaicism has been demonstrated, by means of very deep sequencing, in patients presenting with typical CAPS and Blau syndromes, but negative for germline mutations 25 26…”

Section: Introductionmentioning

confidence: 99%

Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases

et al. 2015

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The present gene panel has resulted suitable for molecular diagnosis of SAIDs. Moreover, genotype-phenotype correlation has confirmed that the interpretation of NGS data in patients with an undefined inflammatory phenotype is remarkably difficult, thus supporting the need of evidence-based and validated clinical criteria to be used concurrently with the genetic analysis for the final diagnosis and classification of patients with SAIDs.

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Somatic NOD2 mosaicism in Blau syndrome

Cited by 63 publications

References 9 publications

Autoinflammatory diseases: update on classification diagnosis and management

Autoinflammatory diseases: update on classification diagnosis and management

Advances in clinical immunology in 2015

Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases

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