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Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients. Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger. Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA. Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4. [ABSTRACT FROM AUTHOR]

The article offers a study that reveals Hereditary angioedema, an autosomal dominant deficiency of C1‐inhibitor (C1‐INH‐HAE). Topics discussed include disease that rises bradykinin‐mediated edema in face, trunk, extremities, and gastrointestinal tract; mentions the outcomes of Hereditary angioedema as asphyxiation, unnecessary emergency abdominal surgeries, and a considerably diminished quality of life; and information on establishing the screening program to optimize diagnosis.

Objective: Hereditary Angioedema (HAE) is a rare autosomal dominant disorder that is caused by improper quantitative level or C1-inhibitor function and these lead to the HAE type I and type II, respectively. C1-inhibitor is a serine protease inhibitor, which controls the activation of complement system and regulation of the fibrinolytic, contact and coagulation systems. C1-inhibitor gene (SERPING1) is located in the q12-q13.1 sub-region of chromosome 11 and consists of eight exons. The aim of this study is genetic diagnosis of HAE type I patients. Material and Methods: The patients who referred to Immunology, Asthma & Allergy Research institute (IAARI) between Jan 2006 to Jan 2014 with clinical phenotype of HAE (subcutaneous angioedema, abdominal pain, laryngeal edema), were entered this study. Twenty HAE type I patients were evaluated for genetic analysis of SERPING1 gene based on low levels of C4 and C1-inhibitor. Blood samples were obtained from these patients and after the DNA extraction from EDTA treated blood samples, polymerase chain reaction (PCR) was accomplished for coding exons (exon 2 to 8) of SERPING1 gene and PCR products were sequenced and the results were analyzed by Finch TV program. Results: Among twenty patients from 15 families with HAE type I, 9 mutations in SERPING1 gene were identified in 12 patients. All mutations were in heterozygous state except one new homozygous missense mutation (c.440T>A) in a patient. The others including one splicing defect (c.51+2T>C) in intron 2, three frame shift mutations in exon four (c.650delG) and exon 8 (c.1356_1357delTG, c.1264delT), three missense mutations in exon 2 (c.5C>T), and exon 8 (c.1477G>A, c.1442T>C), and one nonsense (c.1480C>T) mutation in exon 8 which are previously reported. Conclusion: HAE is a life-threatening disease, and if laryngeal edema occurs possibly leads to death. Therefore, early genetic diagnosis in the families who carries the mutation with symptomatic or asymptomatic phenotype of disease could be helpful for prevention of acute edema and proper treatment in HAE patients and other family members. [ABSTRACT FROM AUTHOR]

Objective: Hereditary Angioedema (HAE) is a rare autosomal dominant disorder caused by low serum levels (type I) or dysfunction (type II) of C1 Inhibitor (C1INH), which is characterized by subcutaneous and/ or submucosal edema attacks involving face, limbs, genitalia, gastrointestinal and respiratory system. HAE could give rise to fatal laryngeal edema, acute abdominal pain leading to unnecessary emergency surgeries, and reduced quality of life. Therefore, the aim of this study was to investigate and report the demographic, clinical and laboratory findings of patients registered in Iranian HAE registry (IHAER). Material and Methods: The patients referred (2006-2016) to Immunology, Asthma and Allergy Research Institute (IAARI) with symptoms suggestive of HAE were investigated (after signing informed consent form) using a questionnaire and laboratory tests. The patients with a definite diagnosis of HAE (type I, II) based on low serum levels of C4 and C1INH quantity/quality accompanying with suggestive clinical findings (after ruling out other possible etiologies) were enrolled into this study. Moreover, in some cases genetic analysis reconfirmed laboratory results. Results: Among 80 patients registered in IHAER with definite diagnosis of HAE (Type I, II; 48.8%, 51.3%) 30 patients belonged to children and adolescents group (aged ≤ 21). The median symptoms age-onset and median diagnostic delay were 11 (min, max; 1, 72) and seven (min, max; 0, 39) years, respectively. Physical trauma (69.7%) and emotional stress (57.6%) were found to be the most common triggers of attacks; however, 82% of patients reported spontaneous attacks as well. The most commonly involved sites were face and limbs. Moreover, laryngeal edema was reported in 56.1% of patients leading to death in three patients during this study. Conclusion: HAE is a life-threatening disease diagnosed with significant delay possibly due to mistaking it for other disorders causing similar symptoms such as acute face and limbs edema. On the other hand, complete avoidance of emotional and physical stress as common HAE triggers could not be easily achieved. Thus, the outcomes of IHEAR in the form of scientific papers/reports is meant to inform health care providers, and policy makers about this rare disease, which would in turns, help with an earlier diagnosis, and improvement in patient care and quality of life. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by Cl-INH (Cl esterase inhibitor), low serum levels (type I), dysfunction (type II) or normal serum levels and function (type III), which lead to subcutaneous and submucosal edema attacks. The aim of this study was to investigate the demographic, clinical and laboratory findings of Iranian patients with HAE. Methods: The patients with a history or symptoms of angioedema who were referred to Immunology, Asthma and Allergy Research Institute (IAARI) between Jan 2006 and Jan 2014, were assessed based on a specific questionnaire and laboratory evaluation. The patients with a definite diagnosis of HAE type I and type II were entered into this study. Results: Among 51 patients, 63.3% were diagnosed with HAE type I and 36.7% with HAE type II. Fifteen patients were under 18 years and 36 were adults. The mean age of symptoms onset and diagnosis were 12.33 ± 10.20 years and 24.48 ± 14.64 years, respectively. The mean delay of diagnosis was 11.02 ± 11.60 years. The most commonly involved locations of edema were hands, face and genitalia. Moreover, laryngeal edema was observed in 61.2% of patients, which led to death in two patients during this study. Conclusion: Hereditary angioedema is a life threatening disease with considerable morbidity and mortality. The outcomes of this study can be used to inform clinicians and health care providers about HAE, which can help earlier diagnosis and better management of the patients, specifically in life threatening attacks. [ABSTRACT FROM AUTHOR]