Segregation of Trans Mutations in the Gene in an Emirati Family with Sensorineural Hearing Loss.

Background/objectives: Hearing loss (HL) is a significant global health concern, affecting approximately 1 in every 1000 newborns, with over half of these cases attributed to genetic factors. This study focuses on identifying the genetic basis of autosomal recessive non-syndromic hearing loss (ARNSHL) in a consanguineous Emirati family.

Methods: Clinical exome sequencing (CES) was performed on affected members of the family, followed by Sanger sequencing to validate the findings.

Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including , , and .

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS.

Impact of missense mutations on the structure-function relationship of human succinyl-CoA synthetase using in silico analysis.

The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with succinyl-CoA synthetase (SCS) deficiency caused by pathogenic variants in genes encoding its two subunits. SCS is a mitochondrial enzyme involved in several metabolic pathways and acts as a heterodimer composed of α and β subunits encoded by SUCLG1 and SUCLA2 genes, respectively. The purpose of this study was to analyze the effects of the most pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) by applying, using different prediction tools, a filtering strategy, on the 343 and 365 nsSNPs found in SUCLG1 and SUCLA2 genes, respectively, retrieved from the databases, then to evaluate their structural and functional effects using homology modeling and molecular docking.

Congenital anomalies of the kidney and urinary tract.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) refer to a range of conditions that affect the kidney and urinary tract. These anomalies can be severe, such as kidney agenesis, or milder, such as vesicoureteral reflux. CAKUT affects over 1% of live births and accounts for 40-50% of cases of chronic kidney failure in children.

Genetic analysis of 106 sporadic cases with hearing loss in the UAE population.

Background: Hereditary hearing loss is a rare hereditary condition that has a significant presence in consanguineous populations. Despite its prevalence, hearing loss is marked by substantial genetic diversity, which poses challenges for diagnosis and screening, particularly in cases with no clear family history or when the impact of the genetic variant requires functional analysis, such as in the case of missense mutations and UTR variants. The advent of next-generation sequencing (NGS) has transformed the identification of genes and variants linked to various conditions, including hearing loss.

The Segregation of p.Arg68Ter- Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the Gene.

Hearing impairment, a rare inherited condition, is notably prevalent in populations with high rates of consanguinity. The most common form observed globally is autosomal recessive non-syndromic hearing loss. Despite its prevalence, this genetic disorder is characterized by a substantial genetic diversity, making diagnosis and screening challenging.

Mitochondrial genes modulate the phenotypic expression of congenital scoliosis syndrome caused by mutations in the TBXT gene.

Background: Congenital scoliosis (CS) is a spinal disorder caused by genetic-congenital vertebral malformations and may be associated with other congenital defects or may occur alone. It is genetically heterogeneous and numerous genes contributing to this disease have been identified. In addition, CS has a wide range of phenotypic and genotypic variability, which has been explained by the intervention of genetic factors like modifiers and environment genes.

Expanding the genetic and phenotypic spectrum of TRAPPC9 and MID2-related neurodevelopmental disabilities: report of two novel mutations, 3D-modelling, and molecular docking studies.

Intellectual disabilities (ID) and autism spectrum disorders (ASD) have a variety of etiologies, including environmental and genetic factors. Our study reports a psychiatric clinical investigation and a molecular analysis using whole exome sequencing (WES) of two siblings with ID and ASD from a consanguineous family. Bioinformatic prediction and molecular docking analysis were also carried out.

Molecular and in silico investigation of a novel ECHS1 gene mutation in a consanguine family with short-chain enoyl-CoA hydratase deficiency and Mt-DNA depletion: effect on trimer assembly and catalytic activity.

Short-chain enoyl-CoA hydratase deficiency (ECHS1D) is a rare congenital metabolic disorder that follows an autosomal recessive inheritance pattern. It is caused by mutations in the ECHS1 gene, which encodes a mitochondrial enzyme involved in the second step of mitochondrial β-oxidation of fatty acids. The main characteristics of the disease are severe developmental delay, regression, seizures, neurodegeneration, high blood lactate, and a brain MRI pattern consistent with Leigh syndrome.

Highly efficient, label free, ultrafast plasmonic SERS biosensor (silver nanoarrays/Si) to detect GJB2 gene expressed deafness mutations in real time validated with PCR studies.

Rapid diagnostics of any gene mutations related to organ loss is highly demanded now-a days to consume time as well to reduce cost. Currently, Surface enhanced Raman spectroscopy (SERS) is evolved to be a rapid investigating tool to screen gene mutations down to single molecule sensing with regard to the design and development of substrates used for sensing. The current research focuses on particular towards direct detection of deafness mutations associated with single and dual sites related to GJB2 gene.

A Novel Mutation in the MAP7D3 Gene in Two Siblings with Severe Intellectual Disability and Autistic Traits: Concurrent Assessment of BDNF Functional Polymorphism, X-Inactivation and Oxidative Stress to Explain Disease Severity.

Intellectual disabilities (ID) and autism spectrum disorders (ASD) are characterized by extreme genetic and phenotypic heterogeneity. However, understanding this heterogeneity is difficult due to the intricate interplay among multiple interconnected genes, epigenetic factors, oxidative stress, and environmental factors. Employing next-generation sequencing (NGS), we revealed the genetic cause of ID and autistic traits in two patients from a consanguineous family followed by segregation analysis.

A novel homozygous PIGO mutation associated with severe infantile epileptic encephalopathy, profound developmental delay and psychomotor retardation: structural and 3D modelling investigations and genotype-phenotype correlation.

The PIGO gene encodes the GPI-ethanolamine phosphate transferase 3, which is crucial for the final synthetic step of the glycosylphosphatidylinositol-anchor serving to attach various proteins to their cell surface. These proteins are intrinsic for normal neuronal and embryonic development. In the current research work, a clinical investigation was conducted on a patient from a consanguineous family suffering from epileptic encephalopathy, characterized by severe seizures, developmental delay, hypotonia, ataxia and hyperphosphatasia.

Loss-of-function mutations in MYO15A and OTOF cause non-syndromic hearing loss in two Yemeni families.

Background: Hearing loss is a rare hereditary deficit that is rather common among consanguineous populations. Autosomal recessive non-syndromic hearing loss is the predominant form of hearing loss worldwide. Although prevalent, hearing loss is extremely heterogeneous and poses a pitfall in terms of diagnosis and screening.

Case report: Functional analysis of the p.Arg507Trp variant of the gene supporting the moderate epilepsy phenotype of mutations in the C-terminal region.

Pathogenic germline variants in the gene are associated with the "multiple congenital anomalies-hypotonia-seizures syndrome 3" (MCAHS3) phenotype. So far, fifty patients have been reported, most of whom suffer from intractable epilepsy. Recently, a comprehensive analysis of a cohort of 26 patients with variants has broadened the phenotypical spectrum and indicated that both p.

Functional consequences of Genetics variant in and within a United Arab Emirates family with Pre-lingual hearing loss.

Hearing loss (HL) is the most prevalent sensory disorder whose etiology comes from environmental and/or genetic factors. Approximately 60 % of HL cases are due to mutations in genes responsible for maintaining a normal hearing function. Despite the monogenic inheritance of hereditary hearing loss (HHL), its diagnosis is challenging as both clinical and genetic heterogeneity characterizes it.

First description of the MEGDEHL syndrome in the Tunisian population via whole-exome sequencing: Novel nonsense mutation in SERAC1 gene.

Introduction: MEGDEL syndrome is a rare recessive disorder, with about 100 cases reported worldwide, which is defined by 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E) and Leigh-like syndrome (L). When these manifestations were added to hepatopathy (H), the syndrome was labelled as MEGD(H)EL. Mutations in SERAC1 gene encoding a serine active site containing 1 protein were described in patients affected by this syndrome.

miR-623 Targets Metalloproteinase-1 and Attenuates Extravasation of Brain Metastatic Triple-Negative Breast Cancer Cells.

Background: Most breast cancer-related deaths result from metastasis. Understanding the molecular basis of metastasis is needed for the development of effective targeted and preventive strategies. Matrix metalloproteinase-1 (MMP1) plays an important role in brain metastasis (BM) of triple-negative breast cancer (TNBC) by promoting extravasation of cancer cells across the brain endothelium (BE).

A novel thymidine phosphorylase mutation in a family with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Molecular docking, dynamic simulation and computational investigations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; OMIM 603041) is a rare inherited metabolic disorder mostly caused by mutations in TYMP gene encoding thymidine phosphorylase (TP) protein that affects the mitochondrial nucleotide metabolism. TP, functionally active as a homodimer, is involved in the salvage pathway of pyrimidine nucleosides. MNGIE-like syndrome having an overlapping phenotype of MNGIE was also described and has been associated with mutations in POLG and RRM2B genes.

Identification of a novel homozygous mutation in NAXE gene associated with early-onset progressive encephalopathy by whole-exome sequencing: in silico protein structure characterization, molecular docking, and dynamic simulation.

Progressive encephalopathy with brain edema and/or leukoencephalopathy, PEBEL1, is a severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration associated with a febrile illness. PEBEL1 is a lethal encephalopathy caused by NAXE gene mutations. Here we report a 6-month-old boy with mitochondrial encephalomyopathy from a consanguineous family.

miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability.

Background: The brain endothelial barrier permeability is governed by tight and adherens junction protein complexes that restrict paracellular permeability at the blood-brain barrier (BBB). Dysfunction of the inter-endothelial junctions has been implicated in neurological disorders such as multiple sclerosis, stroke and Alzheimer's disease. The molecular mechanisms underlying junctional dysfunction during BBB impairment remain elusive.

Further insights into the spectrum phenotype of TRAPPC9 and CDK5RAP2 genes, segregating independently in a large Tunisian family with intellectual disability and microcephaly.

Intellectual disability (ID) often co-occurs with other neurologic phenotypes making molecular diagnosis more challenging particularly in consanguineous populations with the co-segregation of more than one ID-related gene in some cases. In this study, we investigated the phenotype of three patients from a large Tunisian family with significant ID phenotypic variability and microcephaly and performed a clinical exome sequencing in two cases. We identified, within the first branch, a homozygous variant in the TRAPPC9 gene (p.

Genetic Diversity in Casein Gene Cluster in a Dromedary Camel () Population from the United Arab Emirates.

Genetic polymorphisms, causing variation in casein genes (, , , and , have been extensively studied in goats and cows, but there are only few studies reported in camels. Therefore, we aimed to identify alleles with functional roles in the United Arab Emirates dromedary camel ( population to complement previous studies conducted on the same species. Using targeted next-generation sequencing, we sequenced all genes in the casein gene cluster in 93 female camels to identify and characterize novel gene variants.

Molecular insights into kinase domain variants explain variability in both severity and progression of DFNB30 hearing impairment.

Hereditary hearing impairment (HI) is a common disease with the highest incidence among sensory defects. Several genes have been identified to affect stereocilia structure causing HI, including the unconventional myosin3A. Interestingly, we noticed that variants in gene have been previously found to cause variable HI onset and severity.

Whole exome sequencing, in silico and functional studies confirm the association of the mutation p.Cys169Tyr with deafness and suggest a role for the gene in the hearing process.

The development of next generation sequencing techniques has facilitated the detection of mutations at an unprecedented rate. These efficient tools have been particularly beneficial for extremely heterogeneous disorders such as autosomal recessive non-syndromic hearing loss, the most common form of genetic deafness. mutations are the most common cause of hereditary hearing loss.

Genetic etiology of hereditary hearing loss in the Gulf Cooperation Council countries.

The past 30 years have seen an exponential growth concerning the identification of genes and variants responsible for hereditary hearing loss (HL) worldwide. This has led to a huge gain in our understanding of molecular mechanisms of hearing and deafness, which improved diagnosis for populations with hereditary HL. Many communities around the world, especially in the Middle East and North Africa, have a high prevalence of consanguineous marriages.