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Background: 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., Methods: 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., Results: 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., Conclusion: 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.

Background: Hearing impairment (HI) is a heterogeneous disorder. GJB2 and GJB6 genes are typically the first line of genetic screening before proceeding to any massive parallel sequencing. We evaluated the clinical utility of GJB2 and GJB6 testing in the Iranian population. Methods: GJB2 and GJB6 were sequenced. PubMed and Google Scholar were searched for Iranian publications on deletions in the DFNB1 locus. Results: We detected mutations of GJB2 in 16.5%, and no mutations of GJB6. Literature review revealed no reports of mutations of GJB6 in the Iranian population. Conclusion: This data and literature reviews indicate that GJB6 is not commonly responsible for Iranian nonsyndromic HI. Hence, the clinical utility of GJB6 genetic analysis as a first line for HI evaluation does not have the same utility as GJB2 . The study is consistent with recent studies emphasizing the role of ethnicity in the selection of HI genetic testing strategy.

Background: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections., Objectives: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients., Methods: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively., Results: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described., Conclusion: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.

Huntington's disease (HD) is an inherited autosomal neurodegenerative disease caused by the abnormal expansion of the CAG repeats in the Huntingtin (Htt) gene. It has been proven that mitochondrial dysfunction is contributed to the pathogenesis of Huntington's disease. The mitochondrial displacement loop (D-loop) is proven to accumulate mutations at a higher rate than other regions of mtDNA. Thus, we hypothesized that specific SNPs in the D-loop may contribute to the pathogenesis of Huntington's disease. In the present study, 30 patients with Huntington's disease and 463 healthy controls were evaluated for mitochondrial mutation sites within the D-loop region using PCR-sequencing method. Sequence analysis revealed 35 variations in HD group from Cambridge Mitochondrial Sequences. A significant difference (p < 0.05) was seen between patients and control group in eight SNPs. Polymorphisms at C16069T, T16126C, T16189C, T16519C and C16223T were correlated with an increased risk of HD while SNPs at C16150T, T16086C and T16195C were associated with a decreased risk of Huntington's disease.

Several genetic factors are involved with recurrent pregnancy loss (RPL). However, few attempts have been made to associate mitochondrial DNA (mtDNA) variations with RPL. Therefore, we investigated the possible effect of the T4216C mutation in the mitochondrial NADH dehydrogenase I (ND1) gene of 33 women with RPL and 100 controls, using polymerase chain reaction amplification and DNA sequence analysis. Our results showed a statistically significant association of the T4216C mutation (p <  0.05) between patients and controls, which are 30% and 11%, respectively. In conclusion, more research is essentially needed to understand the effect and role of the T4216C mutation in the progress of RPL, which may vary among individuals and different ethnic groups.

We present a patient with non-syndromic and sensorineural hearing impairment with a novel mitochondrial DNA transition. A 7-year-old boy showed progressive deafness. He gradually lost his hearing ability and his hearing function did not improve with hearing aids. Laboratory data revealed normal blood lactate and pyruvate levels. Genetic analyses for mitochondrial DNA and GJB2 and GJB6 genes were performed. Mitochondrial genes analysis revealed a novel heteroplasmic nucleotide substitution, m.628C>T, in the phenylalanine transfer RNA gene. This case study reveals m.628C>T transition as a novel mitochondrial nucleotide change which may be important in mitochondrial deafness.

Objective: Comprehensive sequencing of the coding exons of the calcium-sensing receptor gene (CASR) was performed in a group of Iranian recurrent calcium kidney stone-formers and the results were compared with a control group., Material and Methods: Serum and urine parameters were evaluated in 99 males aged between 30 and 55 years old with idiopathic recurrent calcium urolithiasis and in 107 men as a control group. Products of polymerase chain reaction were sequenced using forward primer until a mutation was found in that exon. Then, other cases were analysed by single-strand conformation polymorphism., Results: Four polymorphisms were detected in CASR exons, all in the coding region of exon 7. These polymorphisms and their minor allele frequency were P748P (100%), A986S (1%), R990G (3%) and E1011Q (98%). There was a significantly higher count of 986S (p = 0.006), 990G (p = 0.006) and E1011 (p = 0.02) alleles in patients. The odds ratio (95% confidence interval) was 2.55 (1.31-4.96) in those at risk of stone disease for the 986S allele and 8.06 (1.80-35.9) for the 990G allele. Men with the RR genotype at R990G showed a significantly higher serum ionized calcium than the RG or GG group (p = 0.03). A significantly lower serum total calcium was found in subjects with the QQ than the EQ genotype with respect to the 1011 locus (p = 0.005). Furthermore, the 1011Q allele was marginally associated with hypercalciuria (p = 0.05)., Conclusion: The 986S, 990G and 1011Q alleles were associated with a recurrent calcium kidney stone-forming state. 986S and 1011Q alleles, but not 986S, were associated with hypercalcaemia.