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).

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.

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.

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.

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.

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.

Report of Hermansky-Pudlak Syndrome in Two Families with Novel Variants in and Genes.

Hermansky-Pudlak syndrome (HSP) was first reported in 1959 as oculocutaneous albinism with bleeding abnormalities, and now consists of 11 distinct heterogenic genetic disorders that are caused by mutations in four protein complexes: AP-3, BLOC1, BLOC2, and BLOC3. Most of the patients show albinism and a bleeding diathesis; additional features may present depending on the nature of a defective protein complex. The subtypes 3 and 4 have been known for mutations in and genes, respectively.

Adult-Onset Hereditary Spastic Paraplegia 15 in a Saudi Patient with A Compound Heterozygous Variant in the Gene.

Hereditary spastic paraplegia (HSP) 15 is an autosomal recessive neurodegenerative disease caused by homozygous or heterozygous point mutations in the gene that encodes the spastizin protein, located on chromosome 14q22-q24. Hereditary spastic paraplegia has been rarely reported in Saudi Arabia. In this article, we reported a rare case of adult-onset HSP 15 with a pure form of the disease in a Saudi patient with a compound heterozygous variant in the gene.

Whole-Exome Sequencing Identifies Novel and Genes Mutations in the Cohort of Saudi Patients With Epilepsy.

Epilepsy is a neurological disorder described as recurrent seizures mild to severe convulsions along with conscious loss. There are many different genetic anomalies or non-genetic conditions that affect the brain and cause epilepsy. The exact cause of epilepsy is unknown so far.

Next-Generation Sequencing Reveals Novel Homozygous Missense Variant c.934T > C in Gene Causing Leukodystrophy and Hypomyelinating Disease.

Leukodystrophies are a diverse group of genetically established disorders categorized by unusual white matter changes on brain imaging. Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect myelin sheath development in the brain. These disorders are categorized as developmental delay, spasticity, hypotonia, and intellectual disabilities.

Clinical whole exome sequencing revealed heterozygous stop-gain and missense variants in the gene associated with epilepsy in Saudi families.

Intellectual disability and developmental encephalopathies are mostly linked with infant epilepsy. Epileptic encephalopathy is a term that is used to define association between developmental delay and epilepsy. Mutations in the (Syntaxin-binding protein 1) gene have been previously reported in association with multiple severe early epileptic encephalopathies along with many neurodevelopmental disorders.

Whole-Exome Sequencing Reveals a Missense Variant c.1612C>T (p.Arg538Cys) in the Gene Leading to Neuromyelitis Optica Spectrum Disorder in Saudi Families.

Biotinidase deficiency is an autosomal recessive, multiple carboxylase deficiency usually associated with seizures, eczema, hypotonia, visual disturbances, hearing loss, and developmental delays. Only a handful of cases of biotinidase deficiency that had clinical features of neuromyelitis optica spectrum disorder have been reported in the literature. The case report study is about the clinical and genetic features of two pediatric patients from different families with biotinidase deficiency whose brain and spine MRI scans were suggestive of neuromyelitis optica.

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics.

SARS-CoV-2 is the causative agent for coronavirus disease-19 (COVID-19) and belongs to the family Coronaviridae that causes sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients. The gene expression profiles of COVID-19 infection models can be used to decipher potential therapeutics for COVID-19 and related pathologies, such as Neuro-COVID. Here, we used the raw RNA-seq reads (Single-End) in quadruplicates derived using Illumina Next Seq 500 from SARS-CoV-infected primary human bronchial epithelium (NHBE) and mock-treated NHBE cells obtained from the Gene Expression Omnibus (GEO) (GSE147507), and the quality control (QC) was evaluated using the CLC Genomics Workbench 20.

Whole Exome Sequencing Identifies Three Novel Mutations in the Gene From Saudi Families Leading to Primary Microcephaly.

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental defect that is characterized by reduced head circumference at birth along with non-progressive intellectual disability. Till date, 25 genes related to MCPH have been reported so far in humans. The (abnormal spindle-like, microcephaly-associated) gene is among the most frequently mutated MCPH gene.

Next generation sequencing reveals novel homozygous frameshift in and splice acceptor variants in gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly.

Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.

A Novel Variant in CWF19L1 Gene in a Family with Late-Onset Autosomal Recessive Cerebellar Ataxia 17.

Introduction: Previously published studies demonstrated that mutations in cause early-onset autosomal recessive cerebellar ataxia 17. In this article, we report a novel homozygous missense variant in in two sisters who had late-onset cerebellar ataxia with epilepsy and describe their clinical and neuroradiological findings.

Methods: We included two female patients with typical symptoms of cerebellar ataxia supported by the MRI findings.

A Novel Intronic Variant in Gene in a Saudi Patient with Myoclonic Epilepsy.

Cerebral metabolism is primarily dependent on glucose for which a facilitated diffusion by glucose transporter protein 1 (GLUT1) across the blood-brain barrier is crucial. This GLUT1 is encoded by the gene. Mutations in will lead to a variety of symptoms known as GLUT1 deficiency syndrome.