Aetiology, risk factors and treatment of typical and atypical pressure ulcers in patients with traumatic brain injury: A narrative review.

Pressure ulcers are one of the leading complications in bedridden patients that result in multiple burdens on healthcare systems and patients (11 billion dollars/year). The prevalence of pressure ulcers in traumatic brain injury patients is 1.5-fold compared with the other bedridden patients. Moreover, critical traumatic brain injury patients who are admitted to the intensive care unit experience severe pressure ulcers and further complications. The motor/sensory disabilities and low supplementation and oxygenation to the pressured side were the main mechanisms of the typical pressure ulcers. Intellectual evaluation is the first essential step to prevent the development of pressure ulcers in high-risk patients. Till now, different scales, including Injury Scale Score and Braden Scale Score, have been provided to assess the pressure ulcer. Since low stages of pressure ulcers heal rapidly, traumatic brain injury patients require a periodical assessment to prevent further developments timely. Alongside different procedures provided to prevent and treat any pressure ulcer, traumatic brain injury patients required additional specific protections. For the first line, fast and efficient rehabilitation repairs motor/sensory disabilities and decreases the chance of pressure ulcer. Our review indicated that pressure ulcer in traumatic brain injury had several complex mechanisms that demand special care. Therefore, further studies are required to address these mechanisms and prevent their progression to typical and atypical pressure ulcers.

An inappropriate decline in ribosome levels drives a diverse set of neurodevelopmental disorders.

Many neurodevelopmental defects are linked to perturbations in genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions in ribosome biogenesis can result in tissue and developmental specific defects remains a mystery. Here we describe new allelic variants in the ribosome biogenesis factor AIRIM primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic analysis, single-cell transcriptome analysis across multiple developmental stages, and single organoid translatome analysis, we identify a previously unappreciated mechanism linking changes in ribosome levels and the timing of cell fate specification during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic approaches ameliorates the growth and developmental defects associated with intellectual disability linked variants, identifying potential treatment options for specific brain ribosomopathies. This work reveals the cellular and molecular origins of protein synthesis defect-related disorders of human brain development. Highlights: AIRIM variants reduce ribosome levels specifically in neural progenitor cells. Inappropriately low ribosome levels cause a transient delay in radial glia fate commitment.Reduced ribosome levels impair translation of a selected subset of mRNAs.Genetic and pharmacologic activation of mTORC1 suppresses AIRIM-linked phenotypes.

Integrated whole transcriptome profiling revealed a convoluted circular RNA-based competing endogenous RNAs regulatory network in colorectal cancer.

Recently, it has been identified that circRNAs can act as miRNA sponge to regulate gene expression in various types of cancers, associating them with cancer initiation and progression. The present study aims to identify colorectal cancer-related circRNAs and the underpinning mechanisms of circRNA/miRNA/mRNA networks in the development and progress of Colorectal Cancer. Differentially expressed circRNAs, miRNAs, and mRNAs were identified in GEO microarray datasets using the Limma package of R. The analysis of differentially expressed circRNAs resulted in 23 upregulated and 31 downregulated circRNAs. CeRNAs networks were constructed by intersecting the results of predicted and experimentally validated databases, circbank and miRWalk, and by performing DEMs and DEGs analysis using Cytoscape. Next, functional enrichment analysis was performed for DEGs included in ceRNA networks. Followed by survival analysis, expression profile assessment using TCGA and GEO data, and ROC curve analysis we identified a ceRNA sub-networks that revealed the potential regulatory effect of hsa_circ_0001955 and hsa_circ_0071681 on survival-related genes, namely KLF4, MYC, CCNA2, RACGAP1, and CD44. Overall, we constructed a convoluted regulatory network and outlined its likely mechanisms of action in CRC, which may contribute to the development of more effective approaches for early diagnosis, prognosis, and treatment of CRC.

The association of RBX1 and BAMBI gene expression with oocyte maturation in PCOS women.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that affects 6-20% of women of reproductive age. One of the symptoms of PCOS is hyperandrogenism, which can impair follicular development. This disruption can cause issues with the development of oocytes and the growth of embryos. Although the exact cause of PCOS is not yet fully understood, studying the gene expression pattern of cumulus cells, which play a crucial role in the maturation and quality of oocytes, could help identify the genes associated with oocyte maturation in PCOS women. Through indirect activation of APC/Cdc20, RBX1 enables oocytes to bypass the GV (germinal vesicles) stage and advance to the MII (metaphase II) stage. our other gene is the BAMBI gene which stimulates WNT signaling, that is a crucial pathway for healthy ovarian function. This study aims to explore the expression level of the RBX1 and BAMBI genes between GV and MII oocytes of PCOS and non-PCOS groups. METHODS: In this experiment, we gathered the cumulus cells of MII (38 cases and 33 control) and GV (38 cases and 33 control) oocytes from women with/without PCOS. Besides, quantitative RT-PCR was used to assess the semi-quantitative expression of BAMBI and RBX1. RESULTS: According to our research, the expression level of RBX1 and BAMBI in MII and GV cumulus cells of PCOS patients was significantly lower than that in non-PCOS ones. CONCLUSION: This research raises the possibility of RBX1 and BAMBI involvement in oocyte quality in PCOS women.

Novel nucleotide variations in the thrombomodulin (THBD) gene involved in coagulation pathways can increase the risk of recurrent pregnancy loss (RPL).

Recurrent pregnancy loss (RPL) is a common but complex complication in fertility conditions, affecting about 15-20% of couples. Although several causes have been proposed for RPL, it occurs in about 35-60% of cases without a known explanation. A strong assumption is that genetic factors play a role in the etiology and pathophysiology of PRL. Therefore, several genes are proposed as candidates in the pathogenesis of RPL. The current study aimed to investigate the effects of nucleotide changes in the THBD (thrombomodulin) gene as an RPL-related candidate gene. This gene encodes a cell receptor for thrombin and is involved in reproductive loss in RPL cases. Its involvement in the natural anticoagulant system has been extensively studied. By genetic screening of the entire coding and noncoding regions of the THBD gene, we found twenty-seven heterozygous and homozygous nucleotide changes. Ten of them led to amino acid substitutions, seven variants were identified in the promoter region, and eight of them occurred in 3'UTR. Potentially, the pathogenicity effects of these variations on THBD protein were evaluated by several prediction tools. The numerous genomic variations prompted noticeable modifications of the protein's structural and functional properties. Furthermore, in-silico scores were consistent with deleterious effects for these mutations. The results of this study provide genetic information that will be useful in the future for clinicians, scientists, and students to understand the unknown causes of RPL better. It may also pave the way for developing diagnostic/prognostic approaches to help treat PRL patients.

Analysis of death risk factors among COVID-19 patients in Yazd, Iran: A case-cohort study.

Background: The COVID-19 epidemic control has become a global challenge and many contributing variables are still unknown to policymakers. This case-cohort study was conducted to investigate the risk factors of mortality in COVID-19 patients. Methods: This case-cohort study was conducted on 956 samples in Ardakan and Meybod counties, Yazd Province, between February 20 and May 20, 2020. The data collection tool was a researcher-made questionnaire. Data analysis was done using descriptive statistics and paired t-test, chi-square, and logistic regression analysis. Results: Of a total cohort population of 993 in Ardakan and Meybod counties, 435 were assigned to the control group and 521 were assigned to the case group. The results of outcome analysis showed that 14.4% of the patients in the case group and 11.5% of the patients in the control group died. According to the results of logistic regression analysis in COVID-19 patients, each one-year increase in age increased the risk of mortality by 6% (HR = 1.06, p < 0.001), each one-day increase in the hospital stay increased the risk of death by 8% (HR = 1.08, p < 0.001). Moreover, the presence of cardiovascular disease, chronic neurological disease, and chronic pulmonary disease increased the risk of death. The patients who underwent mechanical ventilation had 85% less chance of survival (HR = 0.15, p < 0.001). Conclusions: The results showed a higher mortality rate in the elderly patients as well as those with underlying diseases. Attention should be paid to at-risk and elderly patients in terms of ensuring a healthy diet, improving their self-care practices, and providing long-term medical and healthcare facilities.

Investigating the impacts of socio-economic vulnerability indicators on COVID-19: A case study of Yazd, Iran.

Socio-economic vulnerability plays a major role in affected countries by disasters and emergencies. This study aims to identify the most effective socio-economic vulnerability indicators on COVID-19 cases and severity in the Yazd city. This study was conducted in 2022. Regarding purpose of study, different methods were applied during this research. They were including reviewing scientific research, expert panel sessions, weighting the socio-economic vulnerability indicators by Analytic Hierarchy Process (AHP) and examining the spatially relationships between vulnerability indicators and COVID-19. Excel and GIS software were applied for data analysis using local correlation coefficient. AHP analysis showed that employment, population density, buildings quality and distance from hospitals were obtained the most weight in the related indicators of socio-economic vulnerability. GIS mapping overlying showed that four socio-economic vulnerability sub indicators including percentage of immigrants, age, population density and distance from health centers had spatially relationships with COVID-19 cases and severity. Western, northern and some central regions of Yazd were identified as the COVID-19 hot spots. Local officials and health authorities should pay immediate attention to the most influential socio-econimic vulnerability indicators that are dominant in the Yazd city. They incorporate measures to the regions identified as hot spots because people who located in these areas are more vulnerable to COVID-19 and the other future natual or man-made disasters.

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.

Association study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 variants in Iranian women with premature ovarian insufficiency: A case-control study.

Background: Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease. Objective: This study aims to investigate the polymorphisms of rs243865 in the matrix metallopeptidase 2 (MMP2) gene and rs2234693 and rs9340799 in the estrogen receptor 1 (ESR1) gene with susceptibility to POI in Iranian women under 35 yr. Materials and Methods: This case-control study was performed on 150 women with POI and 150 healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020. The genotyping of ESR1 rs9340799, rs2234693, and MMP2 rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software. Results: Our study revealed the frequency of rs243865 TT, CC genotypes in the MMP2 gene and rs2234693 CC, TT; and rs9340799 GG, AA in the ESR1 gene were more prevalent in the case group compared to the control group. In addition, ESR1 rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the ESR1 gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI. Conclusion: ESR1 rs2234693 and rs9340799 polymorphism were strongly associated with our population's POI.

Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.

Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families.

BACKGROUND: Intellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole-exome sequencing (WES)-based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700 genes have been reported in syndromic and non-syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear. METHODS: Whole-exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and in silico analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate-to-severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10 years. RESULTS: Filtering the data identified by WES, two novel homozygous missense variants in FBXO31 and TIMM50 genes and one previously reported mutation in the CEP290 gene in the probands were found. Sanger sequencing confirmed the homozygote variant's presence of TIMM50 and FBXO31 genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability. CONCLUSION: Hence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.

Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder.

BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Here, we established BCAS3 loss-of-function variants as causative for a neurodevelopmental disorder. We report 15 individuals from eight unrelated families with germline bi-allelic loss-of-function variants in BCAS3. All probands share a global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures. The human phenotype is less severe compared with the Bcas3 knockout mouse model and cannot be explained by angiogenic defects alone. Consistent with being loss-of-function alleles, we observed absence of BCAS3 in probands' primary fibroblasts. By comparing the transcriptomic and proteomic data based on probands' fibroblasts with those of the knockout mouse model, we identified similar dysregulated pathways resulting from over-representation analysis, while the dysregulation of some proposed key interactors could not be confirmed. Together with the results from a tissue-specific Drosophila loss-of-function model, we demonstrate a vital role for BCAS3 in neural tissue development.

The effect of regular resistance exercise, vitamin D, and calcium supplements on the gastrocnemius muscle in rats in the post-menopausal period: An experimental study.

BACKGROUND: Menopause is the natural termination of menstruation which affects the quality and important aspects of women's life. OBJECTIVE: To evaluate the effect of regular resistance training (Ex) with vitamin D (Vit. D) and calcium (Ca) supplements in the postmenopausal period on muscle tissue in rats. MATERIALS AND METHODS: In this experimental study, 72 female Wistar rats (8-10-wk old) were randomly divided into control, placebo, Vit. D, Ca, Ex, Ca + Vit. D, Ex + Ca, Ex + Vit. D, and Ex + Ca + Vit. D groups. Control and placebo groups were fed with a standard diet and sesame oil, respectively. Two month after the ovariectomy, Ex, Ca (35 mg/kg), and Vit. D (10000 IU) were administred in all groups except the control. The number of muscle and inflammatory cells, fiber diameter, endomysium thickness, and degenerative collagen fiber area were assessed through hematoxylin-eosin staining. RESULTS: Muscle cell number was increased in the Ex + Vit. D + Ca, Vit. D + Ex, and Vit. D groups compared to the control group; also, inflammatory cell number showed significant increase in the Ex + Vit. D + Ca (12 ± 5.46), Vit. D + Ex (14 ± 3.25), Ex (13 ± 4.08), Vit. D (11 ± 3.26), Ca + Vit. D (10 ± 1.01), and Ca + Ex (9 ± 2.87) groups. Muscle fiber diameter in the Ex + Vit. D + Ca and Vit. D + Ex groups was higher than the other groups. Endomysium thickness was significantly decreased in the Ex + Vit. D + Ca and Vit. D + Ex groups compared to the control and placebo groups (p < 0.001). Degenerative collagen fiber area showed a significant increase in the Ex + Vit. D + Ca and Vit. D + Ex groups (p ≤ 0.001) comparison with the control group. CONCLUSION: Regular resistance exercise, Vit. D, and Ca supplements can improve muscle morphological features in the postmenopausal period.

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.

Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene.

Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: Relationship with NF-KappaB gene expression / Evaluación de los niveles de expresión de miR-181b y miR-126-5p en pacientes con DMT2 comparados con personas sanas: relación con la expresión del gen NF- kappaB

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder whose prevalence is rising very fast across the world. Diagnosis of this disease in early stages (pre-diabetic stage) plays an important role in reducing mortality associated with this disorder. miRNAs, as key players in the pathogenesis of T2DM, have been investigated in several studies. Furthermore, their expression profile changes in the early stages of diabetes mellitus in body fluids such as serum, peripheral blood, and peripheral blood mononuclear cell (PBMC) have been studied. Due to their high stability and the presence of non-invasive sensitive methods for their measurement, such as real-time PCR, they can be used for early diagnosis of T2DM as a biomarker. In this experimental study, the expression levels of miR-181b, miR-126-5p, and NF-KappaB were measured in patients with T2DM, pre-diabetic subjects, and healthy controls in a Yazd population. MATERIAL AND METHOD: Ninety asymptomatic subjects including 30 T2DM, 30 pre-diabetic, and 30 healthy subjects (diagnosis based on WHO criteria) were included in this study. Real-time PCR was used to measure the expression levels of miR-181b and miR-126-5p. Moreover, the NF-KappaB expression level was also measured to determine its relationship with these two microRNAs. RESULT: In this study, the expression level of miR-181b and miR-126-p decreased gradually in pre-diabetic as well as T2DM subjects compared to healthy controls. Furthermore, our study showed a significant negative correlation between these two miRNAs and NF-KappaB for the first time. CONCLUSION: These results introduce these anti-inflammatory miRNAs as powerful tools for early diagnosis of T2DM

ANTECEDENTES: La diabetes mellitus tipo 2 (DMT2) es un trastorno metabólico progresivo cuya prevalencia aumenta muy rápidamente en todo el mundo. El diagnóstico de esta enfermedad en estadios iniciales (fase prediabética) tiene un papel importante para reducir la mortalidad asociada con este trastorno. Los miARN, como elementos clave en la patogenia de la DMT2, se han investigado en varios estudios. Además, se han estudiado los cambios de su perfil de expresión en los estadios iniciales de la diabetes mellitus en líquidos corporales como el suero, la sangre periférica y las células mononucleares de sangre periférica (CMSP). Gracias a su elevada estabilidad y a la existencia de métodos sensibles no invasivos para medirlos, como la RCP en tiempo real, pueden utilizarse como biomarcadores para el diagnóstico precoz de la DMT2. En este estudio experimental se determinaron los niveles de expresión de miR-181b, miR-126-5p y NF-kappaB en pacientes con DMT2, sujetos prediabéticos y controles sanos de una población de la ciudad de Yazd. MATERIAL Y MÉTODO: Se incluyeron en este estudio a 90 sujetos asintomáticos, incluidos 30 con DMT2, 30 prediabéticos y 30 sanos (el diagnóstico se basó en los criterios de la OMS). Se utilizó RCP en tiempo real para determinar los niveles de expresión de miR-181b y miR-126-5p. Se midió también el nivel de expresión de NF-kappaB para determinar su relación con estos 2 micro-ARN. RESULTADOS: En este estudio, el nivel de expresión de miR-181b y miR-126-5p descendió gradualmente en los sujetos prediabéticos y con DMT2 comparados con los controles sanos. Además, nuestro estudio mostró por primera vez una correlación negativa importante entre estos 2 miARN y NF-kappaB. CONCLUSIÓN: Estos resultados sugieren que estos miARN antiinflamatorios son herramientas potentes para el diagnóstico precoz de la DMT2

Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran.

Warburg Micro syndrome and Martsolf syndrome are phenotypically overlapping autosomal recessive conditions characterized by multiple organ abnormalities involving the ocular, nervous, and endocrine systems. Warburg Micro syndrome, the more severe of the two conditions, is caused by loss of function mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20 genes, whereas Martsolf syndrome has been attributed to less damaging mutations in RAB3GAP1 and RAB3GAP2 genes. We report the clinical description and molecular characterization of a consanguineous Iranian family with two siblings, a male and a female, with dysmorphic features, bilateral congenital cataracts, optic nerve atrophy, congenital glaucoma, mild to moderate intellectual disability, seizures, hypogonadism, and mild osteoporosis. Spastic quadriplegia with contractures was observed in the male patient, while the female patient showed only mild hyperreflexia. Magnetic resonance imaging scans performed in the male patient showed a normal brain structure. Both siblings had neither microcephaly nor postnatal growth retardation. Whole exome sequencing identified a novel homozygous nonsense mutation [c.1060C>T; p.(Arg354Ter)] in the TBC1D20 gene in both siblings and confirmed the heterozygous carrier status of both parents. This report describes a novel mutation in the TBC1D20 gene in two Iranian patients with Martsolf syndrome, further extending the allelic heterogeneity and phenotypic spectrum of this rare condition. The genotype and phenotype of the patients are compared with those of Martsolf syndrome and Warburg Micro syndrome patients reported in the literature.

Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: Relationship with NF-κB gene expression.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder whose prevalence is rising very fast across the world. Diagnosis of this disease in early stages (pre-diabetic stage) plays an important role in reducing mortality associated with this disorder. miRNAs, as key players in the pathogenesis of T2DM, have been investigated in several studies. Furthermore, their expression profile changes in the early stages of diabetes mellitus in body fluids such as serum, peripheral blood, and peripheral blood mononuclear cell (PBMC) have been studied. Due to their high stability and the presence of non-invasive sensitive methods for their measurement, such as real-time PCR, they can be used for early diagnosis of T2DM as a biomarker. In this experimental study, the expression levels of miR-181b, miR-126-5p, and NF-κB were measured in patients with T2DM, pre-diabetic subjects, and healthy controls in a Yazd population. MATERIAL AND METHOD: Ninety asymptomatic subjects including 30 T2DM, 30 pre-diabetic, and 30 healthy subjects (diagnosis based on WHO criteria) were included in this study. Real-time PCR was used to measure the expression levels of miR-181b and miR-126-5p. Moreover, the NF-κB expression level was also measured to determine its relationship with these two microRNAs. RESULT: In this study, the expression level of miR-181b and miR-126-p decreased gradually in pre-diabetic as well as T2DM subjects compared to healthy controls. Furthermore, our study showed a significant negative correlation between these two miRNAs and NF-κB for the first time. CONCLUSION: These results introduce these anti-inflammatory miRNAs as powerful tools for early diagnosis of T2DM.

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development.

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 µ g/ml; reference range 1.1-1.9). In Plasma amino acid analysis, there was a significant elevated levels of alanine (3,004 µ mol/L; reference range, 236-410 µ mol/L), glutamine (2,256 µ mol/L; reference range, 20-107 µ mol/L), asparagine (126 µ mol/L; reference range, 30-69 µ mol/L), glutamic acid (356 µ mol/L; reference range, 14-192 µ mol/L), aspartic acid (123 µ mol/L; reference range, 0-24 µ mol/L), and lysine (342 µ mol/L; reference range, 114-269 µ mol/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.