Mutational spectrum and geno‐phenotype correlation in <scp>C</scp>hinese families with <scp>H</scp>ereditary <scp>A</scp>ngioedema

Xu, Yingyang; Zhi, Yuxiang; Yin, Jia; Wang, L. L.; Wen, Liping; Gu, Jie; Guan, Kaopeng; Craig, Timothy J.; Zhang, H. Y.

doi:10.1111/all.12024

Cited by 41 publications

(39 citation statements)

References 22 publications

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“…All these studies have mainly focused on missense mutations, and the groups were divided as “missense” and “other type of SERPING1 defects.” Unlike these studies, we defined every mutation type as a different group and tried to examine the effects of each mutation type on the clinical phenotype. Although the mutation type had no effect on the symptom severity, patients with missense mutation had the highest C1 inhibitor antigenic level, as reported by Xu et al [10]. Patients with large deletion and nonsense mutation had the lowest C1 inhibitor antigenic level (Fig.…”

Section: Discussionsupporting

confidence: 66%

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Gökmen

Gülbahar

Önay

et al. 2018

Int Arch Allergy Immunol

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Background: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. Methods: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. Results: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0–18.7; 5.8%, 0–16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11–78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = –0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = –0.404, p = 0.001) and more frequent annual attacks (r = –0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. Conclusion: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.

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Section: Discussionsupporting

confidence: 66%

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Gökmen

Gülbahar

Önay

et al. 2018

Int Arch Allergy Immunol

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“…No significant linear correlation was found between C1‐INH functional activity and disease severity score (Spearman's r coefficient: −0.31, P = 0.049) or age at first attack (Spearman's r coefficient: 0.15, P = 0.362). According to the type of mutation (Xu et al., ), patients were classified as carrying potentially deleterious mutations (missense and in‐frame variants, excluding mutations at Arg444; group 1) or with disease‐causative mutations (nonsense, frameshift, and mutations on P1 residue; group 2). As reported in Table , clinical parameters, that is, C1‐INH antigen level/functional activity and severity score, were not significantly different between the two groups.…”

Section: Resultsmentioning

confidence: 99%

“…Spearman's correlation analysis was used to evaluate the correlation between C1‐INH serum levels of antigen and functional activity and clinical severity score. Based on the type of C1NH mutation identified, patients were divided into two groups as previously described (Xu et al., ) and a two‐sample t ‐test was used to evaluate serum levels of C1‐INH antigen and functional activity, and severity score differences between groups.…”

Section: Methodsmentioning

confidence: 99%

Mutational Spectrum of the C1 Inhibitor Gene in a Cohort of Italian Patients with Hereditary Angioedema: Description of Nine Novel Mutations

Bafunno

Bova

Loffredo

et al. 2014

Annals of Human Genetics

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SummaryHereditary angioedema (HAE) is an autosomal dominant disease due to mutations in the C1 inhibitor gene (C1NH) that affects protein synthesis (HAE type I) or function (HAE type II). In 45 subjects affected by HAE diagnosed through clinical features and C1 inhibitor deficiency from the south of Italy (38 with type I and 7 with type II HAE), the whole C1NH coding region was screened for mutations by direct DNA sequencing. A severity score based on clinical manifestation, age at disease onset, and need for long-term prophylaxis was used to investigate possible genotype-phenotype correlations. A series of 22 different mutations was identified: nine missense (40.9%), five nonsense (22.7%), six frameshift (27.3), one small deletion (4.5%), and one splicing defect (4.5%). Nine C1NH mutations have not been previously described. No correlation was found between C1 inhibitor function level and severity score or age at first attack. Moreover, there was no correlation between different types of mutations and clinical phenotype. The number of different mutations identified highlights the heterogeneity of C1 inhibitor deficiency and supports the hypothesis that HAE clinical phenotype is not strictly related to the type of mutation but rather depends on unknown factors.

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“…Mutation analyses in Brazil (18), Denmark (19), China (20), and other countries have shown the diversity of mutations in the C1-INH gene and their impact on C1-INH levels, but there seems to be little correlation between the type of mutation and severity of symptoms. Surprisingly, the observation that the sense of smell is impaired in many patients with HAE was first reported in 2011.…”

mentioning

confidence: 99%

The EAACI/GA²LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update

Zuberbier

Aberer

Asero

et al. 2014

Allergy

957

860

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This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

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Mutational spectrum and geno‐phenotype correlation in Chinese families with Hereditary Angioedema

Abstract: It appears that nonsense, frameshift, and mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense and in-frame mutations; however, it does not affect severity of symptoms.

Cited by 41 publications

References 22 publications

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Mutational Spectrum of the C1 Inhibitor Gene in a Cohort of Italian Patients with Hereditary Angioedema: Description of Nine Novel Mutations

The EAACI/GA²LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update

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Mutational spectrum and geno‐phenotype correlation in Chinese families with Hereditary Angioedema

Abstract: It appears that nonsense, frameshift, and mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense and in-frame mutations; however, it does not affect severity of symptoms.

Cited by 41 publications

References 22 publications

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Mutational Spectrum of the C1 Inhibitor Gene in a Cohort of Italian Patients with Hereditary Angioedema: Description of Nine Novel Mutations

The EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update

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The EAACI/GA²LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update