Is there any relationship between mutation in CPS1 Gene and pregnancy loss?

Background: Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific enzyme with the lowest enzymatic rate, which determines the overall rate of the other reactions in the pathway that converts ammonia to carbamoyl phosphate in the first step of the urea cycle. Carbamoyl phosphate synthetase 1 deficiency (CPS1D), which usually presents as lethal hyperammonemia, is a rare autosomal recessive hereditary disease. Case: We report a case of a two-day-old female neonate with lethal hyperammonemia. The newborn infant was presented with hyperammonemia (34.7 μg/ml; reference range 1.1–1.9). In Plasma amino acid analysis, there was a significant elevated levels of alanine (3,004 μmol/L; reference range, 236–410 μmol/L), glutamine (2,256 μmol/L; reference range, 20–107 μmol/L), asparagine (126 μmol/L; reference range, 30–69 μmol/L), glutamic acid (356 μmol/L; reference range, 14–192 μmol/L), aspartic acid (123 μmol/L; reference range, 0–24 μmol/L), and lysine (342 μmol/L; reference range, 114–269 μmol/L). We cannot diagnose the urea cycle disorder (UCD) CPS1D properly only based on the quantity of biochemical intermediary metabolites to exclude other UCDs with similar symptoms. Following next generation sequencing determined one homozygous mutation in CPS1 gene and also this mutation was determined in her parents. The identified mutation was c.2758G > C; p.Asp920His, in the 23 exon of CPS1. This novel homozygous mutation had not been reported previously. Conclusion: We applied whole exome sequencing successfully to diagnose the patient with CPS1D in a clinical setting. This result supports the clinical applicability of whole exome sequencing for cost-effective molecular diagnosis of UCDs

A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms

The association of the paraoxonase 1 Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD

IntroductionThe present study aimed to investigate the association of the paraoxonase 1 (PON1) Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.MethodsThis cross-sectional study was conducted on 428 patients undergoing angiography. The data related to demographic information and physical activity were collected by valid and reliable questionnaires. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. The Gensini and SYNTAX score, anthropometric measurements, and biochemical and clinical parameters were measured by standard protocols.Results and discussionFindings indicated that the odds of obesity was significantly higher in people with the RR genotype compared to the QQ genotype carriers (OR: 2.95 CI: 1.25–6.93, P = 0.014) and also odds of low high-density lipoprotein cholesterol (HDL-C) was marginally higher (OR: 2.31 CI: 0.97–5.49, P = 0.056). There was no significant association between other CAD risk factors with PON1 Q192R polymorphism (P > 0.05). Further analysis showed a significant interaction between sex and 192QR (P = 0.019) and 192 RR (P = 0.007) genotypes on body mass index (BMI). More specifically, the risk of obesity in men carrying the RR genotype was 3.38 times (OR: 3.38 CI: 1.08–10.58, P = 0.036). Also, a significant joint effect of the RR genotype and sex on HDL-C was seen (P = 0.003). The stratification based on sex showed that the risk of low HDL-C is significantly higher in women carrying the RR genotype (OR: 6.18 CI: 1.21–31.46, P = 0.028). A marginal sex-genotype interaction was also found in the risk of elevated alanine aminotransferase (ALT) (P = 0.057). In summary, the findings showed that the risk of obesity and low HDL-C was higher in people carrying the RR genotype. On the other hand, a Q192R polymorphism-sex interaction was observed on the risk of obesity, elevated ALT, and low HDL-C

Association of NFKB1 gene polymorphism (rs28362491) with cardiometabolic risk factor in patients undergoing coronary angiography

Introduction: Genetic and environmental factors are involved in the pathogenesis of cardiovascular diseases (CVDs). The aim of the study was to investigate between the genotype of the NFKB1 gene and the cardiometabolic risk factor in patients undergoing coronary angiography. Methods: This cross-sectional study was conducted on 462 adults (male and women) aged between 35 and 75 years who referred to Afshar Hospital for coronary angiography in 2021- 2022. The polymerase chain reaction restriction fragment length polymorphism method was used to detect the genotype of rs28362491. Biochemical parameters were measured using commercial kits. Gensini and Syntax scores were calculated using the angiography result to assess the extent of coronary artery stenosis. We used multivariate logistic regression analysis to examine the relationship between genotype variants and cardiometabolic risk factors. Results: There was no association between variant genotypes and abnormally levels of serum alanine aminotransferase (ALT) (P value=0.51), aspartate aminotransferase (AST) (P value=0.99), triglyceride (TG) (P value=0.48), total cholesterol (P value=0.79), low density lipoprotein-cholestero (LDL-C) (P value=0.31), high-density lipoprotein-cholesterol (HDL-C) (P value=0.53), fast blood sugar (FBS) (P value=0.39), systolic blood pressure (P value=0.14), diastolic blood pressure (P value=0.64), Gensini score (P value=0.48) and syntax score (P value=0.74) in the crude model even after adjustment for confounding factors. Conclusion: We found no association between the ATTG polymorphism and cardiometabolic risk factors in patients who had coronary angiography. Further investigations are needed to assess the association between variants of 28362491 and cardiometabolic markers

GGPS1-associated muscular dystrophy with and without hearing loss

Ultra-rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra-rare missense variants in GGPS1 and provide follow-up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease-causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1-associated muscular dystrophy

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2-48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course

Genetic Susceptibility to Transient and Permanent Neonatal Diabetes Mellitus

Neonatal diabetes mellitus (NDM) is a rare kind of diabetes characterized by hyperglycemia and low levels of insulin. Clinically, it is categorized into two main types: transient NDM (TNDM) and permanent NDM (PNDM). These types are diagnosed based on duration of insulin dependence early in the disease. In TNDM, diabetes begins in the first few weeks of life with remission in a few months. However, infant with PNDM have insulin secretory failure in the late fetal or early post-natal period with no remission. Mutation in the KCNJ11 and ABCC8 genes can cause both TNDM and PNDM, and infant with this mutation can respond to transition from insulin to sulfonylureas making identification of genes involved in the disease important for appropriate treatment

Type 1 early infantile epileptic encephalopathy: A case report and literature review

Abstract Background Variants in the Aristaless‐related homeobox (ARX) gene lead to a variety of phenotypes, with intellectual disability being a steady feature. Other features can include severe epilepsy, spasticity, movement disorders, hydranencephaly, and ambiguous genitalia in males. X‐linked Ohtahara syndrome or Type 1 early infantile epileptic encephalopathy (EIEE1) is a severe early‐onset epileptic encephalopathy with arrested psychomotor development caused by hemizygous mutations in the ARX gene, which encodes a transcription factor in fundamental brain developmental processes. Methods We presented a case report of a 2‐year‐old boy who exhibited symptoms such as microcephaly, seizures, and severe multifocal epileptic abnormalities, and genetic techniques such as autozygosity mapping, Sanger sequencing, and whole‐exome sequencing. Results We confirmed that the patient had the NM_139058.3:c.84C>A; p.(Cys28Ter) mutation in the ARX gene. Conclusion The patient with EIEE1 had physical symptoms and hypsarrhythmia on electroencephalogram. Genetic testing identified a causative mutation in the ARX gene, emphasizing the role of genetic testing in EIEE diagnosis

Evaluation of Rap1GAP and EPAC1 gene expression in endometriosis disease

Background: Endometriosis is a female reproductive system disease in which the endometrial tissue is found in other women's organs. Various factors are effective in the development of endometriosis, and because of the interaction of genetics and environmental factors, this disease is a multi-factorial disease. MAPK/ERK and PI3K/Akt/mTOR pathways are activated by growth factors and steroid hormones and are known as two important pathways involved in the processes of growth, proliferation, and survival of endometriosis cells. Raps, monomeric GTPase of the Ras family, are able to activate these pathways independent of Ras. The goal of our study was to evaluate the expression level of Rap1GAP and EPAC1 genes as two important RapGAPs (GTPase-activating proteins) and RapGEFs (guanine nucleotide exchange factors), respectively, in endometriosis tissues and normal endometrium tissues. Materials and Methods: In this study, 15 samples of women without signs of endometriosis were taken as control samples. Fifteen ectopic and 15 eutopic samples were taken from women with endometriosis using laparoscopic surgery. The expression of EPAC1 and Rap1GAP genes was investigated by the real-time polymerase chain reaction technique, and the results were analyzed by one-way ANOVA test. Results: EPAC1 upregulated significantly in ectopic tissues compared to eutopic and control tissues. Rap1GAP expression was lower in ectopic tissues compared to control and eutopic tissues. Conclusions: Based on these results, it may be concluded that changes in the expression of the Rap1GAP and Epca1 genes may play a role in the pathways involved in the pathogenesis, displacement, and migration of endometriosis cells

Circulating microRNA-122, microRNA-126-3p and microRNA-146a are associated with inflammation in patients with pre-diabetes and type 2 diabetes mellitus: A case control study

The prevalence of type 2 diabetes mellitus (T2DM) is increasing dramatically worldwide. Dysregulation of microRNA (miRNA) as key regulators of gene expression, has been reported in numerous diseases including diabetes. The aim of this study was to investigate the expression levels of miRNA-122, miRNA-126-3p and miRNA-146a in diabetic and prediabetic patients and in healthy individuals, and to determine whether the changes in the level of these miRNAs are reliable biomarkers in diagnosis, prognosis, and pathogenesis of T2DM. Additionally, we examined the relationship between miRNA levels and plasma concentrations of inflammatory factors including tumor necrosis factor alpha (TNF-α) and interleukin 6 (Il-6) as well as insulin resistance. In this case-control study, participants (n = 90) were allocated to three groups (n = 30/group): T2DM, pre-diabetes and healthy individuals as control (males and females, age: 25-65, body mass index: 25-35). Expression of miRNA was determined by real-time polymerase chain reaction (RT-PCR). Furthermore, plasma concentrations of TNF-α, IL-6 and fasting insulin were measured by enzyme-linked immunosorbent assay. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as an indicator of insulin resistance. MiRNA-122 levels were higher while miRNA-126-3p and miRNA-146a levels were lower in T2DM and pre-diabetic patients compared to control (p\u3c0.05). Furthermore, a positive correlation was found between miRNA-122 expression and TNF-α (r = 0.82), IL-6 (r = 0.83) and insulin resistance (r = 0.8). Conversely, negative correlations were observed between miRNA-126-3p and miRNA-146a levels and TNF-α (r = -0.7 and r = -0.82 respectively), IL-6 (r = -0.65 and r = -0.78 respectively) as well as insulin resistance (r = -0.67 and r = -0.78 respectively) (all p\u3c0.05). Findings of this study suggest the miRNAs can potentially contribute to the pathogenesis of T2DM. Further studies are required to examine the reproducibility of these findings