Novel <i>SERPING1</i> gene mutations and clinical experience of type 1 hereditary angioedema from North India

Jindal, Ankur Kumar; Rawat, Amit; Kaur, Anit; Sharma, Deepak; Gupta, Anju; Garg, Ravinder; Dogra, Sunil; Saikia, Biman; Minz, Ranjana Walker; Singh, Surjit

doi:10.1111/pai.13420

Cited by 14 publications

(19 citation statements)

References 64 publications

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“…There are several reasons for these shortfalls: Our experience with SERPING1 gene sequencing in patients with type 1 HAE at PGIMER in Chandigarh (India) has shown 9 novel (likely pathogenic) and 2 previously reported diseasecausing variants in 11 families where a SERPING1 variant could be detected. No disease-causing variants in SERPING1 gene were detected in 9 other suspected families tested [9]. Thus, in our practice, genetic diagnosis failed to diagnose 9/20 (diagnostic sensitivity of 45%) of those with biochemically proven quantitative C1-INH deficiency, while incautious interpretation of variants of unknown significance might risk false positives, reducing specificity of the test.…”

Section: Diagnosismentioning

confidence: 68%

“…Thus, India illustrates the unfortunate and disparate situation seen for HAE patients in many low-income countries compared with higher-income countries. It has been reported that delays in diagnosis of HAE are very common in India, with a median delay in diagnosis of 6.5 years (range 0-28 years) [9]. Of note, it is very typical for parents or grandparents not to receive their initial diagnosis of HAE until their children or grandchildren begin to have symptoms [9].…”

Section: Diagnosismentioning

confidence: 99%

“…It has been reported that delays in diagnosis of HAE are very common in India, with a median delay in diagnosis of 6.5 years (range 0-28 years) [9]. Of note, it is very typical for parents or grandparents not to receive their initial diagnosis of HAE until their children or grandchildren begin to have symptoms [9]. There are several reasons for these shortfalls: Our experience with SERPING1 gene sequencing in patients with type 1 HAE at PGIMER in Chandigarh (India) has shown 9 novel (likely pathogenic) and 2 previously reported diseasecausing variants in 11 families where a SERPING1 variant could be detected.…”

Section: Diagnosismentioning

confidence: 99%

“…The requirement to attend a healthcare facility makes it impossible for many patients to be treated promptly to achieve an optimal response. At times, the HAE attack may be severe enough that patients/parents may not even have enough time to reach the hospital for getting an FFP infusion emphasizing the dire need for an acute "ondemand" self-administered therapy in these countries [9].…”

Section: Fresh Frozen Plasma For Management Of Attacksmentioning

confidence: 99%

“…Patients with HAE in these countries are frequently managed prophylactically using attenuated androgens or tranexamic acid and for short-term prophylaxis and acute "on-demand" therapy with attenuated androgens and fresh frozen plasma (FFP), respectively. Thus, in these countries, it is not uncommon to see avoidable HAE-related mortality and increased morbidity [9].…”

Section: Introductionmentioning

confidence: 99%

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Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema

Jindal

Reshef

Longhurst

et al. 2021

Clinic Rev Allerg Immunol

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Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin and mucosal edema. The main treatment goal is to enable a “normal life” for all patients. However, due to high costs, there are limited options for the management of HAE in most developing and low-income countries. As a result, most of the recommended first-line treatments are not available. In this review, we attempt to highlight the disparities in health-care resources for the management of patients with HAE amongst different countries. Data was collected from HAE experts in countries who provide tabulated information regarding management and availability of HAE treatments in their countries. We reviewed the two most recent international HAE guidelines. Using India, the world’s second most populous country, as a paradigm for HAE management in lower-income countries, we reviewed the evidence for second-line and non-recommended practices reported by HAE experts. Results suggest significant inequities in provision of HAE services and treatments. HAE patients in low-income countries do not have access to life-saving acute drugs or recently developed highly effective prophylactic medications. Most low-income countries do not have specialized HAE services or diagnostic facilities, resulting in consequent long delays in diagnosis. Suggestions for optimizing the use of limited resources as a basis for future discussion and reaching a global consensus are provided. There is an urgent need to improve HAE services, diagnostics and treatments currently available to lower-income countries. We recommend that all HAE stakeholders support the need for global equity and access to these essential measures.

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Section: Diagnosismentioning

confidence: 68%

Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

Section: Fresh Frozen Plasma For Management Of Attacksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema

Jindal

Reshef

Longhurst

et al. 2021

Clinic Rev Allerg Immunol

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Phenotypic and Genotypic Characterization of Hereditary Angioedema in Saudi Arabia

et al. 2022

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Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

Grombirikova,

Bily,

Soucek

et al. 2023

J Clin Immunol

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Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype–phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

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Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India

Cited by 14 publications

References 64 publications

Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema

Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema

Phenotypic and Genotypic Characterization of Hereditary Angioedema in Saudi Arabia

Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

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