جستجوی مقالات مرتبط با کلیدواژه « point mutation » در نشریات گروه « پزشکی »

Citrullinemia type 1 is an autosomal recessive disease resulting in ammonia accumulation in the blood, and if uncontrolled may progress to coma or death in the early months after birth.

Cases presentation: 

7 families from Southwest Iran having one or more children in their families or relatives, who died in the early months after birth due to citrullinemia type 1 visited for genetic counseling and prenatal diagnosis. Whole-exome sequencing was performed on peripheral blood specimens and chorionic villus samples. Sanger sequencing confirmed the genetic results. Both parents were identified as carriers for the exon 15 c.1168G>A mutation in each family. The fetus in 6 out of 7 families was homozygote for A substitution on the argininosuccinate synthetase 1 gene.

The presence of a common mutation in the argininosuccinate synthetase 1 gene in all affected families of Southwest Iran shows a possible population cluster in this area.

Hemophilia A (HA) is an X-linked recessive bleeding disorder with a high rate of genetic heterogeneity. The present study was conducted on a large cohort of Iranian HA patients and data obtained from databases.

A total of 622 Iranian HA patients from 329 unrelated families who had been referred to a medical genetics laboratory in Tehran from 2005 to 2019, were enrolled in this retrospective, observational study. Genetic screening of pathogenic variants of the F8 gene was performed using inverse shifting PCR, direct sequencing, and multiplex ligation-dependent amplification (MLPA). Point mutation frequencies in different exons were analyzed for our samples as well as 6031 HA patients whose data were recorded in a database.

A total of 144 different pathogenic or likely pathogenic variants including 29 novel variants were identified. A strategy to decrease costs of genetic testing of HA was suggested based on this finding.

This study provides comprehensive information on F8 pathogenic/likely pathogenic variants in Iranian HA patients which improves the spectrum of causative mutations and can be helpful to clinicians and medical geneticists in counseling and molecular diagnosis of HA.

 Peroxisome biogenesis disorders (PBDs) are a group of diseases with peroxisomal dysfunction. Wide range of symptoms are associated with the disease which are due to mutations in the PEX genes. The PEX1 mutation occurs in Zellweger syndrome (ZS), a severe autosomal recessive condition with hypotonia, intellectual disability, and hepatic enlargement. The present study determined the molecular aspects of ZS in a family in South Khorasan Province, Iran.

 Whole-exome sequencing (WES) was performed, clinical history was taken, and the family pedigree was drawn. Subsequently, Sanger sequencing was performed for unique primers. Afterwards, in terms of ZS phenotype, in silico studies were done to examine the changes that occurred in the protein structure.

 The PEX1 (NC_000007.14) mutation was detected at location Chr7q21.2. This chromosomal location was anticipated as the disorder-causing variant. GGT (Glycine) changes to GAT (Aspartate) in codon 843 were confirmed by Sanger sequencing. Examination results of the mentioned family revealed a missense mutation in the PEX1.

 In conclusion, our study indicated a mutation in the PEX1 in the affected family. This mutation is a missense variant at codon 843 in ZS patients. It has an autosomal recessive inheritance pattern. This mutation may be widespread among Iranian population with ZS and can be used for a more desirable personalized medicine.

Although several techniques have been developed for the detection of JAK2 V617F mutation, these techniques have their disadvantages. High-resolution melting (HRM) analysis is a new, post-PCR analysis. Simple and fast, this method is based on PCR melting curve techniques. This study examined the JAK2 V617F mutation by the high-resolution melting method in 20 patients with erythrocytosis, and the results were compared with those obtained from the direct sequencing method. The results showed 100% sensitivity and 100% positive predictive value for this methodology in the patient sample set tested.

Pseudomonas aeruginosa is an opportunistic pathogen of clinical importance, particularly in immunocompromised and burn patients. This bacterium is becoming resistant to many antibiotics via intrinsic or acquired mechanisms. Mutations in anti-mutator genes, such as pfpI, can be a potential intrinsic mechanism of antibiotic resistance. This study aimed to evaluate the possible effects of mutations of this gene on coding proteins of multi-drug resistant P. aeruginosa isolates.

The antibiotic resistance pattern of 50 P. aeruginosa isolates against 9 anti-pseudomonas antibiotics was determined by the disk diffusion method. PCR, followed by sequencing, detected the mutations in the pfpI gene. The retrieved sequences were translated to the corresponding amino acid sequences using an online protein database. The amino acid sequences in mutated isolates were compared with the reference sequence using a multiple alignment method.

Out of 50 isolates, 43 (86%) were resistant to all antibiotics. Sequencing and multiple alignment analyses showed that amino acids in positions 21, 24, and 57 of pfpI gene were changed in resistant isolates, and all these mutations were observed in each isolate. Homology modeling showed that these amino acids were part of a cleft on the protease. The other point mutations resulted in amino acid changes were in positions 67, 83, and 165.

The data obtained in this study showed that the pfpI gene of P. aeruginosa might have a significant effect on response to antibiotics. Further epidemiologic and comprehensive studies are required to confirm these findings.

Helicobacter pylori, a Gram-negative bacteria, is the most important cause of gastric ulcer, gastric malignancies, and chronic gastritis. Clarithromycin is recognized as the most important antibiotic for the treatment. Clarithromycin resistance is related to point mutations in the 23srRNA, and the most important mutation is A2143G, A2142G. The most common cause of resistance to metronidazole is rdxA gene mutational inactivation. This study aimed to evaluate clarithromycin and metronidazole resistance in H. pylori by phenotypic and genotypic methods. In total, 338 gastric biopsy samples were collected. The samples were cultivated on Colombia agar, consisting of various antibiotics and were incubated at 37°C under microaerophilic conditions. The biochemical tests and PCR assay were applied to identify the strains as H. pylori. The E-test was applied in the antibiogram test based on CLSI standard. The PCR-RFLP assay was performed to identify point mutations and followed by sequencing. The PCR method was done to identify deletion of a 200-bp fragment from the rdxA gene. In total, 131 (38.7%) H. pylori strains were isolated that among them, 70 (53.4%) and 83 (63.4%) showed resistance to clarithromycin and metronidazole, respectively. Prevalence of A2143G, A2142G, A2142C mutations were 71.4%, 7.1% and 4.3%, respectively. Seven (8.4%) strains, included 200-bp deletion. The high prevalence of resistance to clarithromycin and metronidazole in H. pylori is a major concern revealed by this study which should be taken into account by physicians in selecting drug regimens. The results confirmed the necessity of phenotypic and genotypic methods of antibiotic susceptibility.

Carney complex (CNC) is a rare genetic disease. Here, we report a case of CNC and explore clinical manifestations and gene mutation studies of CNC. A male patient with CNC at the age of 16 yr was admitted to Affiliated Hospital of Zunyi Medical University in July, 2015. Although the patient had typical signs of Cushing's syndrome, he also presented with certain rare signs of Cushing's syndrome, such as "freckle-like" scattered spots of pigmentation on the face and around the lips. In addition, concomitant severe osteoporosis led to flattened vertebrae and the compression of corresponding levels of the spinal cord. Radiographic findings revealed adrenal nodular hyperplasia. Based on sequencing, 2 novel heterozygous mutations of the PRKAR1A gene were found. CNC was eventually diagnosed via pathologic biopsy. After 1 year of follow-up, the patient exhibited weight loss, relief of low back pain, normal blood biochemical indicators and cortisol levels at the lower limit of the normal range.

Alpha-thalassemia (α-thal) is probably the most prevalent monogenic condition in the world. Deletions are the most common type of mutations in α-thal, followed by point mutations and small insertion/deletion. In the context of national screening program for prevention of thalassemia and hemoglobinopathies in Iran, α-thal carriers have come to more attention. Therefore, the frequency and distribution of α-globin mutations in various regions of the country have been studied in recent years. A comprehensive search was performed in PubMed, Scopus, and national databases for finding reports on mutation detection in α-thal carriers and HbH disease with Iranian origin. The mutation data of 10849 α-thal carriers showed that -α3.7 and α-5NT were the most common deletional and nondeletional mutations, respectively. In HbH disease cases, the -α3.7/--MED was the most prevalent genotype. Overall, 42 different mutations have been identified in α-globin cluster reflecting the high heterogeneity of the mutations in Iranian populations.

Resistance to clarithromycin in Helicobacter pylori has become one of the most important reasons for failure of antibiotic eradication therapies. This resistance is predominantly caused by point mutations in the peptidyl transferase region of 23S rRNA.
The aim of this study was to determine the prevalence of the A2143G, A2144G, and A2143C point mutations among H. pylori strains from gastric biopsy specimens in Bushehr, in the southwest of Iran.
Patients and Gastric biopsy specimens were obtained from patients with upper gastrointestinal symptoms during endoscopy. Fluorescent in situ hybridization (FISH) using oligonucleotide probes was applied to detect the point mutations responsible for clarithromycin resistance in H. pylori.
Of the 135 H. pylori-positive specimens, two harbored strains with the A2143G mutation and nine contained strains with the A2144G mutation. Thus, the prevalences of the A2143G and A2144G point mutations were 1.5% and 6.7%, respectively. The A2143C point mutation was not found.
The prevalences of the point mutations A2143G and A2144G were low in our geographic area. Based on the findings of this study, clarithromycin still seems to be a useful antibiotic for initial treatment regimens in Bushehr, Iran.

Due to the lack of a suitable and economic test for the analysis of the polymorphism at codon 167, we developed a new PCR-RFLP technique, based on a modified forward primer (UT-HC167 MF-primer), to identify simultaneously the SNPs at codons 167 and 200 of isotype 1 β-tubu­lin gene of Haemonchus contortus. There already are several safe and easy methods for identification of point mutations at codons 198 and 200. Due to the lack of a reliable and easy method for the detection of the single nucleo­tide polymorphism (SNP) at codon 167, we developed an innovative PCR-RFLP technique based on a modified forward primer (UT-HC167 MF-primer), in which the nucleotide T at the posi­tion 443 was substituted through a nucleotide A creating a restriction site for restriction endonuc­lease SnaB I in the nucleotide sequences including codon 167. A total of 138 adult male H. contortus were collected from three different geo-climatic areas of Iran. The isolated genomic DNA of each single worm was amplified by PCR using primers flanking codon 167. The PCR product (527 bp) was then amplified by semi-nested PCR using the UT-HC167 MF-primer and the reverse primer achiev­ing a PCR product of 451 bp in length. This PCR product was subsequently digested with the restriction endonucleases SnaB I and TaaI for analysis of the mutations at codons 167 and 200, respec­tively. All worms had two alleles encoding for phenylalanine (BZss homozygote) for both codons. Using the UT-HC167 MF-primer and a suitable reverse primer designed upstream from codon 200, it is possible to amplify a PCR product which can be used for analysis of the SNPs at all three mentioned codons using RFLP.