Analysis of SERPING1 expression on hereditary angioedema patients: Quantitative analysis of full-length and exon 3 splicing variants

Mena, Rocío; López‐Lera, Alberto; López-Trascasa, Margarita

doi:10.1016/j.imlet.2011.07.011

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…In comparison with the healthy control, the expression of C1-INH mRNA remarkably decreased in HAE patients and was only 20% of the normal level on average. This finding was in accordance with the results from several previous works [14][15][16]. However, a Korean study described normal expression of C1-INH mRNA in HAE-1 [17].…”

Section: Discussionsupporting

confidence: 93%

“…Premature termination codons formed by nonsense or frameshift trigger rapid mRNA degradation without being translated [21,22], so mRNA expression is reduced. When considering the mutation types, a significant difference in mRNA levels was observed between healthy controls and patients with nonsense mutations but not in those with missense mutations [14]. It has been hypothesized that missense mutations might impact the posttranslation process [17].…”

Section: Discussionmentioning

confidence: 99%

“…The majority are heterogeneous, with only 10 homogeneous genetic defects reported [13]. However, only a few of them have been evaluated for the expression of SERPING1 mRNA [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene

Zhi

2020

Clin Transl Allergy

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Background Hereditary angioedema with deficient and dysfunctional C1 inhibitor (C1-INH-HAE) is a rare genetic disorder. The majority of the cases with this disease are caused by mutations in the C1-inbitor gene SERPING1 and are classified as type 1 and type 2. We aimed to detect mutations in the SERPING1 gene and evaluate its expression in nine probands with hereditary angioedema from nine different families. Methods Nine probands with hereditary angioedema from nine different families and 53 healthy controls were recruited in this study. All eight exons and intron–exon boundaries in the SERPING1 gene were amplified by PCR and then sequenced. Mutations were identified by alignment with reference sequences. mRNA expression was measured by real-time PCR. Results All probands were diagnosed with HAE type 1. Nine mutations were found in nine patients: c.44delT, c.289C<T, c.296_303delCCATCCAA, c.538C<T, c.786_787insT, c.794 G < A, c.939delT, c.1214_1223delCCAGCCAGGA, and c.1279delC. All mutations formed a premature stop codon that might lead to the impaired synthesis of C1 inhibitor and result in the deficiency of this protein. None of the detected mutations were observed in the controls. In the C1-INH-HAE group, SERPING1 mRNA expression was significantly reduced (20% of the normal average level) compared to controls. Conclusions Three known and six novel mutations in the SERPING1 gene were identified, and they produced a truncated nonfunctional C1 inhibitor without a reactive central loop. All the mutations led to reduced expression of SERPING1 mRNA in peripheral blood and low antigenic C1 inhibitor levels.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene

Zhi

2020

Clin Transl Allergy

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“…Reverse-transcription with oligo-dT primers (Qiagen, Valencia, CA) and quantification using a SYBR Green system (Applied Biosystems, Foster City, CA) were performed as previously described [[14]].…”

Section: Results and Disussionmentioning

confidence: 99%

Expression of the SERPING1 gene is not regulated by promoter hypermethylation in peripheral blood mononuclear cells from patients with hereditary angioedema due to C1-inhibitor deficiency

López-Lera

Pernía

López-Trascasa

et al. 2014

Orphanet J Rare Dis

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SERPING1 mutations causing Hereditary Angioedema type I (HAE-I) due to C1-Inhibitor (C1-INH) deficiency display a dominant-negative effect usually resulting in protein levels far below the expected 50%. To further investigate mechanisms for its reduced expression, we analyzed the promoter DNA methylation status of SERPING1 and its influence on C1-INH expression. Global epigenetic reactivation correlated with C1-INH mRNA synthesis and protein secretion in Huh7 hepatoma cells. However, PBMCs extracted from controls, HAE-I and HAE-II patients presented identical methylation status of the SERPING1 promoter when analyzed by bisulphite sequencing; the proximal CpG island (exon 2) is constitutively unmethylated, while the most distant one (5.7Kb upstream the transcriptional start site) is fully methylated. These results correlate with the methylation profile observed in Huh7 cells and indicate that there is not a direct epigenetic regulation of C1-INH expression in PBMCs specific for each HAE type. Other indirect modes of epigenetic regulation cannot be excluded.

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“…De la Cruz et al found differences in the quantity of this alternative transcript in monocytes between HAE patients depending on the type of mutation, presenting a decrease in the full-length variant in those patients with mutations altering splicing. 7 The existence of this alternative splicing hinders the demonstration of the pathological effect of c.52-10T>A mutation because it also would affect skipping exon 3. However, we have not been able to amplify the full-length transcript in children.…”

Section: Hereditary Angioedema Caused By a Novel Intronic Variant Of Serping1mentioning

confidence: 99%

Hereditary angioedema caused by a novel intronic variant of SERPING1

López-Martínez

Martínez‐Borra

Fernández‐González

et al. 2021

Pediatric Allergy Immunology

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Analysis of SERPING1 expression on hereditary angioedema patients: Quantitative analysis of full-length and exon 3 splicing variants

Cited by 8 publications

References 24 publications

Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene

Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene

Expression of the SERPING1 gene is not regulated by promoter hypermethylation in peripheral blood mononuclear cells from patients with hereditary angioedema due to C1-inhibitor deficiency

Hereditary angioedema caused by a novel intronic variant of SERPING1

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