Clinical whole Exome Sequencing Reveals Novel Homozygous Missense Variant in the Gene causing Autosomal Recessive Spinocerebellar Ataxia.

Background & Objective: Autosomal recessive cerebellar ataxias (ARCA) are rare heterogenous neurodegenerative disorders characterized by degeneration of the cerebellum and spinal cord with an early onset before the age of 20 years. PMPCA (MIM: 613036), is a key enzyme in mitochondrial protein processing which is critical for cell survival and growth. Our objective was to investigate Peptidase, Mitochondrial Processing Subunit Alpha (PMPCA) mutations linked with Spinocerebellar ataxia, autosomal recessive 2 (SCAR2).

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Background: Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control.

Current genetic models for studying congenital heart diseases: Advantages and disadvantages.

Congenital heart disease (CHD) encompasses a diverse range of structural and functional anomalies that affect the heart and the major blood vessels. Epidemiological studies have documented a global increase in CHD prevalence, which can be attributed to advancements in diagnostic technologies. Extensive research has identified a plethora of CHD-related genes, providing insights into the biochemical pathways and molecular mechanisms underlying this pathological state.

Autosomal recessive spinocerebellar ataxia type 4 due to a novel homozygous mutation in the VPS13D gene in a Saudi family.

Vacuolar protein sorting 13 homolog D (VPS13D) gene encodes a protein involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. This study reports a novel homozygous mutation (c.12494T>C p.

Whole exome sequencing of a novel homozygous missense variant in gene leading to Fanconi anaemia complementation group.

Partner and localiser of BRCA2 (), also known as , is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.

Childhood-related neural genotype-phenotype in ATP1A3 mutations: comprehensive analysis.

Background: ATP1A3 is a gene that encodes the ATPase Na + /K + transporting subunit alpha-3 isoenzyme that is widely expressed in GABAergic neurons. It maintains metabolic balance and neurotransmitter movement. These pathways are essential for the proper functioning of the nervous system.

A novel homozygous splice donor variant in the gene causing Leigh syndrome with epilepsy, a French-Canadian disorder in a Saudi family: case report.

Background: The mitochondria are a cellular power house. Tissues are involved in frequent energy consumption, and any failure or irregularity in the continuous energy production could lead to abnormalities. The leucine-rich pentatricopeptide repeat () gene is one of the mitochondrial-related functions genes; variations in these genes are responsible for complex phenotypes that affect many organs such as the brain, liver, and muscles.

Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families.

Background: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport.

Objectives: A molecular diagnostics study of families presenting oculocutaneous albinism.

Exploring bioactive compounds from a symbiotic bacterial strain of Spongiobacter sp.

Marine sponges are a host of different symbiotic groups of bacteria playing crucial roles in the protection and survival of marine sponges. Marine symbiotic bacteria from sponges are promising sources of bioactive chemicals and are increasingly being investigated. Therefore, the present study was undertaken to analyze total compounds from active symbiotic bacterial strain from sponge, .

Leber hereditary optic neuropathy presenting as bilateral visual loss and white matter disease.

Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disorder that typically affects young male adults in their second and third decades of life. It usually manifests as painless, subacute, progressive, bilateral vision loss, with more than 90% of affected individuals losing their vision before age 50. Compared with other diseases that cause optic neuritis (multiple sclerosis or neuromyelitis optica spectrum disorders), LHON has worsening visual function in the first 6-12 months of disease progression, is predominantly male, the optic nerve is affected bilaterally from onset, there is no gadolinium enhancement on MRI, no response to disease-modifying therapy, and there is a family history of mutation in mitochondrial DNA.

Use of whole exome sequencing for identification of genetic variants related to Growth Hormone Deficiency and Short Stature: A Family-Based Study.

Objective: Genetic polymorphisms in genes involved in growth process and Vitamin-D metabolism form a significant etiology behind growth hormone deficiency and short stature. The aim of this study was to explore for known and unknown genes and variants related to growth hormone and short stature in a family based study using whole exome sequencing (WES).

Method: This family-based study included a family with members diagnosed with growth hormone deficiency, short stature and Vitamin-D deficiency (four boys affected and four boys non-affected).

Exploration of potential molecular mechanisms and genotoxicity of anti-cancer drugs using next generation knowledge discovery methods.

Background & Objectives: Accurate identification of molecular and toxicological functions of potential drug candidates is crucial for drug discovery and development. This may aid in the evaluation of the risks of genotoxicity and carcinogenesis. In addition, in silico characterization of existing and new drugs might offer clues for future investigations and aid in the development of anticancer treatments.

Pretreatment with troxerutin protects/improves neurological deficits in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is the major and leading cause of mortality and an alarming public health challenge. TBI leads to permanent cognitive, motor, sensory and psychotic disabilities. Patients suffering from the various and long-term repercussions of TBI currently have limited therapy choices.

Whole exome sequencing identified five novel variants in , , , and leading to epilepsy in consanguineous families.

Epilepsy is a group of neurological disorders characterized by recurring seizures and fits. The Epilepsy genes can be classified into four distinct groups, based on involvement of these genes in different pathways leading to Epilepsy as a phenotype. Genetically the disease has been associated with various pathways, leading to pure epilepsy-related disorders caused by variations, or involving physical or systemic issues along with epilepsy caused by and , or developed by genes that are putatively involved in epilepsy lead by variations.

Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis.

Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the damage site, thus affecting the healing process. The present study aimed to enhance the therapeutic potential of MSCs using combined therapy, along with the novel synthetic compounds of benzimidazol derivatives.

Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan.

Unlabelled: The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division.

Methods: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected.

Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families.

Background: Autosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31.

Role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis.

Objectives: Accurately identifying the cellular, biomolecular, and toxicological functions of anticancer drugs help to decipher the potential risk of genotoxicity and other side effects. Here, we examined bleomycin for cellular, molecular and toxicological mechanisms using next-generation knowledge discovery (NGKD) tools.

Methods: This study was conducted at the Faculty of Applied Medical Sciences, King Abdulaziz University (KAU), Jeddah, Saudi Arabia in October 2022.

A Novel Homozygous Nonsense Variant in the Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family.

(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited.

Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme, Gene in a Saudi Family Causing Salt and Pepper Syndrome.

Salt and pepper developmental regression syndrome (SPDRS) is an autosomal recessive disorder characterized by epilepsy, profound intellectual disability, choreoathetosis, scoliosis, and dermal pigmentation along with dysmorphic facial features. GM3 synthase deficiency is due to any pathogenic mutation in the ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5 () gene, which encodes the sialyltransferase enzyme that synthesizes ganglioside GM3. In this study, the Whole Exome Sequencing (WES) results presented a novel homozygous pathogenic variant, NM_003896.

Novel Variants in , and Cause Charcot-Marie-Tooth and Spastic Ataxia of Charlevoix-Saguenay Type Diseases.

Charcot-Marie-Tooth disease (CMT) and autosomal recessive spastic ataxia of Charlevoix-Saguenay type (ARSACS) are large heterogeneous groups of sensory, neurological genetic disorders characterized by sensory neuropathies, muscular atrophies, abnormal sensory conduction velocities, and ataxia. CMT2EE (OMIM: 618400) is caused by mutations in (OMIM: 137960), CMT4F (OMIM: 614895) is caused by (OMIM: 605725), CMTX1 (OMIM: 302800) is caused by mutations in (OMIM: 304040), and ARSACS (OMIM: 270550) is caused by mutations in (OMIM: 604490). In this study, we enrolled four families: DG-01, BD-06, MR-01, and ICP-RD11, with 16 affected individuals, for clinical and molecular diagnoses.