Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH).

Congenital hypothyroidism (CH) occurs with a relatively alarming prevalence in infants, and if not diagnosed and treated in time, it can have devastating consequences for the development of the nervous system. CH is associated with genetic changes in several genes that encode transcription factors responsible for thyroid development, including mutations in the NK2 homeobox 1 (NKX2.1) gene, which encodes the thyroid transcription factor-1 (TTF-1). Although CH is frequently observed in pediatric populations, there is still a limited understanding of the genetic factors and molecular mechanisms contributing to this disease. The sequence of the NKX2.1 gene was investigated in 75 pediatric patients with CH by polymerase chain reaction (PCR), single-stranded conformation polymorphism (SSCP), and direct DNA sequencing. Four missense heterozygous variations were identified in exon 3 of the NKX2.1 gene, including three novel missense variations, namely c.708A>G, p.Gln202Arg; c.713T>G, p.Tyr204Asp; c.833T>G, p.Tyr244Asp, and a previously reported variant rs781133468 (c.772C>G, p.His223Gln). Importantly, these variations occur in highly conserved residues of the TTF-1 DNA-binding domain and were predicted by bioinformatics analysis to alter the protein structure, with a probable alteration in the protein function. These results indicate that nucleotide changes in the NKX2.1 gene may contribute to CH pathogenesis.

Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) as a colon cancer predisposition syndrome is an autosomal-dominant inherited condition and is diagnosed by the progress of hundreds or thousands of adenomatous colonic polyps in the colon. This study aims at the nature and effect of Adenomatous Polyposis Coli (APC) gene mutations in FAP tumorigenesis. METHODS: The genetic screening of 59 FAP Iranian patients in 10 families was performed by polymerase chain reactions and the direct sequencing of the entire coding exons of the APC gene. To do linkage haplotype analysis and multiplex PCR-based microsatellite examination, six short tandem repeat loci were selected in this gene. To evaluate and predict the potentially deleterious effects, comprehensive bioinformatics pathogenicity assays were used. RESULTS: A total of 12 germline heterozygous and homozygous nucleotide variations were identified. They included two missense mutations, four nonsense mutations, which would lead to the truncated and nonfunctional protein products, four synonymous or silent variations, and two nucleotide deletions of 1 to 5 bp or frameshift mutations. In addition, three novel heterozygous nonsense mutations were found in exons 10, 14, and 15 of the gene. There was also p.Arg653Met as a novel heterozygote mutation in exon 14 of the gene. CONCLUSIONS: Bioinformatics analysis and three-dimensional structural modeling predicted that these missense and nonsense mutations generally are associated with the deleted or truncated domains of APC and have functional importance and mainly affected the APC protein. These findings may provide evidence for the progress of potential biomarkers and help to understand the role of the APC gene in FAP.

Economic Burden of Epidermolysis Bullosa Disease in Iran.

Background: Epidermolysis bullosa (EB) is prevalent in Iran and incurs direct and indirect costs on the health care system and the patient. Therefore, this study was conducted to estimate the economic burden of this disease in Iran. Methods: This study includes all patients with EB disease who had been referred to the medical centers of Iran in 2019-2020 for treatment of their disease, especially Hazrat Fatimah Hospital and their medical records are available in Iran EB Patients Association (IEBPA). In estimating the economic burden of diseases and costing studies, we calculated the average direct and indirect costs for a patient and used it to estimate the costs of the patient population. In this study, a prevalence approach was used to calculate the economic burden of this disease. For this purpose, the existing cases of the disease in 2019-2020 were calculated. The data collected from the questionnaires that were completed through interviews with patients as well as the data extracted from the review of their files were entered into Excel software and analyzed. Results: The total direct medical costs of direct non-medical and indirect are equal to 7.319.428.315 & 5.390.440.775 and 45.875.654.514 Rials respectively, and the total economic burden of the disease and the average of each patient is 58.585.514.604 and 155.890.789 respectively. Conclusion: High indirect costs, especially informal care, represent the socio-economic burden of this disease and constitute more than half of the total indirect costs. Therefore, the obvious gap and hidden social costs of this disease are related to health policymakers, especially when they want to study the impact of this disease on different income classes of families.