Journal of Human Genetics and Genomics
Volume:4 Issue: 1, Jun 2020

In December 2019, the new virus, COVID-19, emerged and led to a pandemic respiratory acute disease. Almost all countries have experienced different rates of morbidity and mortality. These differences can be attributed to factors such as a diagnostic test capacity for COVID-19 and the health system efficiency. Besides the differences between countries related to the COVID-19 management, different patients represent a diverse range of clinical symptoms, from outpatient to patients admitted to the intensive care unit (ICU) due to the severity of symptoms. To gain deeper insights into such disparities in the severity of COVID-19 clinical presentations, epidemiological studies have reported risk factors such as old age, male sex, underlying chronic diseases such as diabetes, inflammatory and cardiovascular diseases, which have a bearing on susceptibility to COVID-19. In addition to these risk factors, the molecular mechanism involved in the virus entry process has been under investigation. Apart from a well-known protein called ACE2 (angiotensin-converting enzyme 2), which plays the receptor role for COVID-19, another essential protein in this pathway is TMPRSS2 (transmembrane protease, serine 2). This protease has a crucial role in effective membrane integration between the virus and the target cell. This process can affect the severity of the infection and the mortality rate of the disease. Thus, it seems that understanding the role of TMPRSS2 in COVID-19 infection can help better management by designing TMPRSS2 inhibitors drugs. Given the variants of the TMPRSS2 gene, which are associated with the severity of symptoms, people exposed to severe forms of this disease can be identified before the deterioration of the disease to adopt appropriate therapeutic approaches. Therefore, this study focused on the different levels of the TMPRSS2 interactions with COVID-19 virus and disease severity.

Hearing loss (HL) is the most prevalent sensory disease in humans. HL is among the most clinically and genetically heterogeneous disorders. Pathogenic variants in GJB2 are the principal cause of HL in many populations. Therefore, GJB2 analysis should be considered as the first step for HL.

This study aimed to find causative variants in the GJB2 gene in 75 unrelated Iranian patients who suffered from Autosomal recessive non-syndromic hearing loss (ARNSHL).

Peripheral blood samples were used for genomic DNA extraction. PCR-direct sequencing was performed to detect GJB2 mutations.

In this study, thirty-four chromosomes (21.33%) carried GJB2 mutations. In general, 10 variants were detected among 19 patients. Seven cases were homozygous for c.35delG; (p.Gly12Valfs*2), two were homozygous for c.71G>A; (p.Trp24*), two were homozygous for c.358-360delGAG (p.Glu120del), and two were homozygous for c.-23+1G>A mutation. One patient was a compound heterozygote for c.35delG and c.-23+1G>A mutations, and another patient with compound heterozygosity for c.290dupA and c.235delC mutations were determined. Four patients carried a mono-allelic variant in the GJB2 including c.126G>T; (p.Glu42Asp), c.23C>T; (p.Thr8Met), c.445G>A; (p.Ala149Thr) and c.269T>C; (p.Leu90Pro). Accordingly, c.35delG mutation was the most common variant in this study.

Finding common variants of HL mutations in different populations can elevate the diagnostic value of molecular testing in the screening of affected individuals, and can improve counselling to minimize the risk of having affected offspring for at-risk couples. Besides, early diagnosis can easily lead to speech development and prevents further problems.

Mesenchymal stem cells (MSCs) have different sources, including bone marrow, adipose tissue, umbilical cord, amniotic fluid, and amniotic membrane. They have immunomodulatory properties. These cells can be used for the treatment of many neurological diseases such as Parkinson’s and Alzheimer’s disease. In this study, MSCs were isolated from the amniotic membrane, and their surface markers were investigated using flow cytometry. MSCs were differentiated to osteoblasts, adipocytes, and finally, to the nerve cells under the influence of epidermal, basic fibroblast natural growth factors, and two other media. The first medium included indomethacin, butyric acid, and ascorbic acid. The second one included retinoic acid and ascorbic acid. The expression of paired box gene 2 (PAX2) and nuclear receptor related-1 (NURR1) genes were investigated using real-time polymerase chain reaction and showed higher levels than that of controls. The presence of the expression of β-tubulin III and microtubule-associated protein 2 (MAPII) was studied by immunocytochemistry. The result suggested that the second medium included retinoic acid was better than the first medium. Protecting neurons are important in neurological diseases, and the expression of mRNAs such as PAX2, NURR1, β-tubulin III, and MAPII plays an effective role in neural differentiation.

Studies have shown that the polymorphism of genes involved in breast cancer in combination with environmental factors has an important role in the progression of breast cancer.

In this study, the association between polymorphism of the ERBB4 gene with breast cancer was investigated.

In the present study, 110 patients with breast cancer and 110 healthy individuals were selected as controls. DNA extraction was performed on patients’ samples. The tetra-ARMS-PCR method was used to study rs13393577 polymorphism. Finally, statistical analysis was performed using SPSS software using t-test.

The results of the study in the patients' group showed that the frequencies of TT, CT, and CC genotypes were 73, 15, and 1.8%, and allelic frequency in this group for T and C alleles were 95 and 5%, respectively. In addition, the results of the study in the control group showed that the frequencies of TT, CT, and CC genotypes were 86, 11, and 0.9%, respectively. The allelic frequencies in the control group for the T and C alleles were 97 and 3%, respectively. In addition, the risk ratio and allelic reliability were obtained for T allele was OR: 3.06: and CI = 0.31 – 29.94 and for C allele was OR: 0.32: and CI: 0.03 - 3.19, respectively. Finally, statistical analysis showed that no significant difference was observed between the two groups (P > 0.05).

The results of the present study showed that rs13393577 polymorphism in the EGFR gene (ERBB4) is not a genetic predisposing factor for breast cancer.

Cystic fibrosis (CF) is known as one of the most common autosomal recessive disorders, which is caused by mucosal glands. A deficiency in the Cystic fibrosis transmembrane conductance regulator gene (CFTR), which encodes a chloride channel, triggers damage to epithelial cells in respiratory ducts, pancreas, intestine, genital ducts in males, liver system, and sweat glands.

This study aimed to conduct the sequencing of 27 exons of the CFTR gene to screen the spectrum of the variants in patients from all over Iran from different ethnicities.

This study is a descriptive-analytical, that was performed for eleven years from 2010 to 2021. Totally 345 patients were referred to Tehran Medical Genetics Laboratory by specialists. These patients were categorized into four groups. The first group included clinically confirmed patients of CF having clinical features and biochemical abnormalities, plus a positive sweat chloride test. The second group included couples with an alive or deceased child affected. The third group included CBAVD (Congenital bilateral absence of the vas deferens) cases, and the fourth group included prenatal diagnoses who were looking for carrier detection, or her spouse is affected with CBAVD.

Fifty-four variants and five deletions were found from 345 patients, the most common frequent variant were c.1521_1523delCTT ([delta]F508) (47 (6.81%)), c.1000C>T (R334W, 31 (4.45%)), c.1911delG (2043delG, 25 (3.62%)), c.2051_2052delAAinsG (2183AA->G, 15 (2.17%)), c.1624G>T (G542X, 12 (1.74%)), c.1697C>A (A566D, 12 (1.74%)), c.1210-12T [5] (9(1.30%)) and c.3196C>T (R1066C,7 (1.01%)) respectively and frequency of other variants were less than 1%. Deletion in some exons was established by MLPA assay, the most common deletion was c. (53+1_54-1) _ (164+1_165-1) del (CFTRdele2, 7 (1.01%)).

This study improves our knowledge concerning carrier analysis and genetic counseling. Also, it helps to develop a cost-effective newborn screening program.