SARS-CoV-2 outbreak in Iran: The dynamics of the epidemic and evidence on two independent introductions.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.

Application of Multiplex Ligation-Dependent Probe Amplification in Determining the Copy Number Alterations of HER Gene Family Members in Invasive Ductal Breast Carcinoma.

BACKGROUND: The aim of this study was to assess the usability of multiplex ligation-dependent probe amplification (MLPA) for copy number determination of HER gene family members (ERBB1-4) in invasive breast carcinoma and to explore the association of ERBB1-4 gene copy numbers with clinicopathological characteristics of breast cancer (BC) patients. METHODS: Clinical and immunohistochemical characteristics were assessed in 104 BC patients and the molecular subtype was determined for each tumor sample. Furthermore, HER-2/neu status was assessed by immunohistochemistry (IHC) and equivocal results were confirmed by Fluorescent in situ hybridization (FISH). The copy numbers of ERBB1-4 genes were determined by MLPA. RESULTS: Twenty-five percent of all patients showed ERBB2 gene-amplification by MLPA, whereas 14.4% of cases showed ERBB-2/neu overproduction at the protein level (IHC). Moreover, only 2.9% and 1.9% of patients showed amplification in ERBB1 and ERBB4, respectively. No copy number changes were observed in ERBB3. Our results indicated a significant association between ERBB2 copy number gain and histological grade (p value= 0.01), stage (p value= 0.02), and tumor subtypes (p value= <0.001). In addition, we found MLPA more accurate in assessing HER2 status with 15.4% and 9.6% gene amplification detection in early stages (1, 2A and 2B) and advanced tumor stages (3A, 3B, and 4), respectively, compared to IHC (early stages= 13.5% and advanced stages= 4.7%). CONCLUSION: According to our findings, MLPA is a fast, precise and low-cost technique to detect ERBB2 amplification, especially in advanced tumor stages. However, due to infrequent amplification found in ERBB1 and ERBB4 as well as the lack of amplification in ERBB3, their importance in the prognostic evaluation of BC patients remains controversial.

The study of association between reduced folate carrier 1 (RFC1) polymorphism and non-syndromic cleft lip/palate in Iranian population.

Introduction: Cleft lip/palate is one of the most common congenital defects and is supposed to have multifactorial etiology, including a complex interaction between genetics and environment. Reduced folate carrier 1 (RFC1) gene takes part in folate transportation within the cells. In this study, the association of A80G polymorphism in the RFC1 gene with the non-syndromic cleft lip/palate (nsCL/P) was investigated in Iranian infants for the first time. Methods: In this case-control survey, 122 Iranian infants with nsCL/P and 164 healthy infants were investigated for RFC1 polymorphism by PCR and RFLP methods. The results were statistically compared with control group, odds ratios with 95% CI were estimated by univariate and multivariate logistic regression model and a P <0.05 was considered statistically significant. Results: The RFC1 G allele was significantly higher (P=0.001; OR=7, 95% CI: 4.7-10.2) in the cases (60.3%) compared with the controls (17.9%). Not only the RFC1 AG genotype was significantly higher (P<0.001; OR=44, 95% CI: 14.6-133) in cases (67.8%) than the controls (27.4%), but also GG genotype (P<0.001; OR=85, 95% CI: 20.5-352) was much higher in cases (26.4%) than the controls (4.3%). Conclusion: Our study indicated that the RFC1 (A80G) polymorphism was associated with the nsCL/P in Iranian population. Moreover, 80GG homozygosity was significant in the cases. The presence of G allele can be considered as a risk factor for the nsCL/P. Infants with the GG and AG genotypes were more prone to cleft lip/palate as compared to the AA ones. This finding emphasizes the role of RFC1 gene and the intracellular levels of folate.

Association of Transforming Growth Factor Alpha Polymorphisms with Nonsyndromic Cleft Lip and Palate in Iranian Population.

BACKGROUND: Cleft lip with or without cleft palate (CL/P) is one of the most common congenital anomalies and the etiology of orofacial clefts is multifactorial. Transforming growth factor alpha (TGFA) is expressed at the medial edge epithelium of fusing palatal shelves during craniofacial development. In this study, the association of two important TGFA gene polymorphisms, BamHI (rs11466297) and RsaI (rs3732248), with CL/P was evaluated in an Iranian population. METHODS: The frequencies of BamHI and RsaI variations were determined in 105 unrelated Iranian subjects with nonsyndromic CL/P and 218 control subjects using PCR and RFLP methods, and the results were compared with healthy controls. A p-value of <0.05 was considered statistically significant. RESULTS: The BamHI AC genotype was significantly higher (p=0.016) in the patients (12.4%) than the control group (5.0%). The BamHI C allele was significantly higher (p=0.001; OR=3.4, 95% CI: 1.6-7.4) in the cases (8.0%) compared with the control group (2.5%). CONCLUSION: Our study showed that there was an association between the TGFA BamHI variation and nonsyndromic CL/P in Iranian population.

A large family with spinocerebellar ataxia type 6 in Iran: a clinical and genetic study.

The authors describe a large Iranian family with autosomal dominant cerebellar ataxia, which included 14 patients in four generations. We examined seven patients who had expanded CAG repeats in the CACNA1A gene with repeat instability (24 and 25 repeats). Although all patients showed cerebellar ataxia, each patient exhibited peripheral neuropathy or spasticity indicating intrafamilial phenotypic variability.