Identification of a New Variant in NLRP3 Gene by Whole Exome Sequencing in a Patient with Cryopyrin-Associated Periodic Syndrome

Vahedi, Mahdieh; Parvaneh, Nima; Vahedi, Saeedeh; Shahrooei, Mohammad; Ziaee, Vahid

doi:10.1155/2021/2023119

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…Our first case had severe joint disease correlated with CINCA syndrome, but CNS manifestations and mental disability were not observed. Our first case also had optic disc edema that is usually presented in CINCA syndrome [ 11 – 15 ].…”

Section: Discussionmentioning

confidence: 97%

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The Efficacy of Anti-Tumor Necrosis Factor Therapy in Cryopyrin-Associated Periodic Syndromes: A Report of Two Cases

Tahghighi

Vahedi

Parvaneh

et al. 2022

Case Reports in Genetics

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Background. Cryopyrin-associated periodic syndromes (CAPSs) are a group of autoinflammatory disorders caused by a mutation in the NLRP3 gene. NLRP3 mutations increase inflammasome activation; therefore, IL-1 targeted therapies are frequently used in the aforementioned disorders. Case Presentation. We report two cases of CAPS in which the diagnosis was confirmed by genetic tests and an evaluation of the therapeutic response to anti-tumor necrosis factor (anti-TNF) agents. Conclusion. IL-1 inhibitors are highly effective in treating CAPS patients. Most patients with severe symptoms such as neurologic involvement improve with IL-1 blockade. Anti-TNF agents might be effective in reducing mild manifestation; however, they are not effective in improving more severe complications.

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Section: Discussionmentioning

confidence: 97%

“…After one month, a considerable response was observed, while full recovery occurred after four months. We reported this case in detail in our previous report [ 11 ].…”

Section: Casementioning

confidence: 99%

The Efficacy of Anti-Tumor Necrosis Factor Therapy in Cryopyrin-Associated Periodic Syndromes: A Report of Two Cases

Tahghighi

Vahedi

Parvaneh

et al. 2022

Case Reports in Genetics

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“…Symptoms the same as NOMID/CINCA syndrome was reported by a few studies. Severe forms of the disease present with macrophage activation syndrome (MAS) and early-onset enterocolitis (4,9,10). In one study the rst presentation of MAS was at 43 years old male (11).…”

Section: Discussionmentioning

confidence: 99%

Challenges in the Diagnosis of Infantile Enterocolitis and RareAuto-inflammatory Syndromes: A Case Report and Literature Review

Khalesi,

Jafari,

Kianifar

et al. 2023

Preprint

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Introduction: Auto-inflammatory syndromes are characterized by systemic inflammation and a broad spectrum of clinical manifestations. The Gastrointestinal mucosa has a critical role in the immune system. Autosomal dominant mutations in the NLRC4 gene have been associated with systemic auto-inflammation and early-onset infantile enterocolitis. The main aim of our study is to highlight the importance of monogenic auto-inflammatory syndromes in early-onset enterocolitis. We provided a literature review of NLRC4-inflammasome-mediated auto-inflammatory disease. Case presentation: This case report described a 3-year-old female child with very early-onset enterocolitis and a missense mutation in exon 4 of the NLRC4 gene. Colonic mucosal biopsy showed colitis. Whole exome sequencing revealed a missense mutation in exon 4 of the NLRC4 gene. Conclusions: Most auto-inflammatory disorders are rare and Patients have always experienced a diagnostic and treatment delay. Intestinal inflammation is one of the clinical presentations of auto-inflammatory syndromes. Auto-inflammatory diseases have a broad spectrum of clinical characteristics, and the gastrointestinal tract is frequently involved. Monogenic auto-inflammatory diseases such as NLRC4 gene mutations should be considered a rare cause of chronic intestinal inflammation and early-onset enterocolitis.

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“…Today, more than 100 NLRP3 variants are classified as pathogenic/likely pathogenic with strong genotype-phenotype correlation along the disease continuum ( 89 ). Most of these variants are missense substitutions mainly concentrated in exon 3 which encodes for the central NACHT domain ( 89 ); some pathogenic variants affecting C-terminal exons encoding for the LRR domain have been also found, as in the recent work of Vahedi et al, in which the authors described a new variant in exon 5, coding for the LRR domain, of the NLRP3 gene (NM-001079821.3: c. 1060 G>T, p.(Ala354Ser) ( 90 ). All these CAPS associated NLRP3 pathogenic variants are gain of function leading to an hyperactivation of NLRP3 inflammasome, an increased secretion and release of pro-inflammatory cytokines and tissue damage related to disease symptoms.…”

Section: The Caps Spectrum: Clinical Laboratory and Genetic Findingsmentioning

confidence: 99%

NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies

2022

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The NLRP3 inflammasome is one of the NOD-like receptor family members with the most functional characterization and acts as a key player in innate immune system, participating in several physiological processes including, among others, the modulation of the immune system response and the coordination of host defences. Activation of the inflammasome is a crucial signaling mechanism that promotes both an acute and a chronic inflammatory response, which can accelerate the production of pro-inflammatory cytokines, mainly Interleukin (IL)-1β and IL-18, leading to an exacerbated inflammatory network. Cryopyrin associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disorder, clinically characterized by cutaneous and systemic, musculoskeletal, and central nervous system inflammation. Gain-of-function mutations in NLRP3 gene are causative of signs and inflammatory symptoms in CAPS patients, in which an abnormal activation of the NLRP3 inflammasome, resulting in an inappropriate release of IL-1β and gasdermin-D-dependent pyroptosis, has been demonstrated both in in vitro and in ex vivo studies. During recent years, two new hereditary NLRP3-related disorders have been described, deafness autosomal dominant 34 (DFN34) and keratitis fugax hereditaria (KFH), with an exclusive cochlear- and anterior eye- restricted autoinflammation, respectively, and caused by mutations in NLRP3 gene, thus expanding the clinical and genetic spectrum of NLRP3-associated autoinflammatory diseases. Several crucial mechanisms involved in the control of activation and regulation of the NLRP3 inflammasome have been identified and researchers took advantage of this to develop novel target therapies with a significant improvement of clinical signs and symptoms of NLRP3-associated diseases. This review provides a broad overview of NLRP3 inflammasome biology with particular emphasis on CAPS, whose clinical, genetic, and therapeutic aspects will be explored in depth. The latest evidence on two “new” diseases, DFN34 and KFH, caused by mutations in NLRP3 is also described.

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Identification of a New Variant in NLRP3 Gene by Whole Exome Sequencing in a Patient with Cryopyrin-Associated Periodic Syndrome

Cited by 4 publications

References 10 publications

The Efficacy of Anti-Tumor Necrosis Factor Therapy in Cryopyrin-Associated Periodic Syndromes: A Report of Two Cases

The Efficacy of Anti-Tumor Necrosis Factor Therapy in Cryopyrin-Associated Periodic Syndromes: A Report of Two Cases

Challenges in the Diagnosis of Infantile Enterocolitis and RareAuto-inflammatory Syndromes: A Case Report and Literature Review

NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies

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