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.

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.

Exome sequencing reveled a compound heterozygous mutations in gene causing developmental delay and primary microcephaly.

RTTN (Rotatin) (OMIM 614833) is a large centrosomal protein coding gene. mutations are responsible for syndromic forms of malformation of brain development, leading to polymicrogyria, microcephaly, primordial dwarfism, seizure along with many other malformations. In this study we have identified a compound heterozygous mutation in gene having NM_173630 c.

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.

Whole exome sequencing reveals a homozygous nonsense mutation in gene leading to Tay-Sachs disease in Saudi Family.

Objective: To study the causative variants in affected member of a Saudi family with Tay-Sachs disorder. This disorder includes paralysis, decreasing in attentiveness, seizures, blindness, motor deterioration progresses rapidly leading to a completely unresponsive state and a cherry-red spot visible on the eye.

Methods: Whole exome sequencing (WES) and Sanger sequencing was performed to study the variant leading to the disease.

A novel variant c.3706C>T p.(Avg 1236Cys) in the gene in a Saudi patient with susceptibility to Alzheimer's disease 9.

Alzheimer's disease (AD) is the most common cause of dementia with around 50 million people suffering from this disease worldwide. Mutations in the ATP-binding cassette sub-family A member 7 () have been reported to cause susceptibility to AD 9 (OMIM #608907). In this study, we report a novel variant in in a Saudi patient with susceptibility to AD 9 and a strong family history of neurodegenerative disorders, which may be explained by the same variant.

Novel Missense Variant in Heterozygous State in the Gene Leading to Intellectual Developmental Disorder With Dysmorphic Facies and Ptosis.

Intellectual developmental disorder with dysmorphic facies and ptosis is an autosomal dominant condition characterized by delayed psychomotor development, intellectual disability, delayed speech, and dysmorphic facial features, mostly ptosis. Heterozygous mutations in bromodomain and plant homeodomain (PHD) finger containing one ( gene have been reported. In this study, whole exome sequencing (WES) was performed as a molecular diagnostic test.

A Novel Heterozygous Variant in Exon 19 of NOTCH3 in a Saudi Family with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL; OMIM #125310) is the most common cause of monogenic familial cerebral small vessel disease. It typically manifests at middle adulthood with highly variable clinical features including migraine with aura, recurrent transient ischemic attacks or ischemic strokes, mood disorders, and progressive cognitive decline. It is caused by mutations in the NOTCH3 gene, which maps to the short arm of chromosome 19 and encode for epidermal growth factor-like repeats.

A novel mutation in gene in a Saudi female with ataxia telangiectasia.

Ataxia telangiectasia is a hereditary multisystem disorder with a wide range of symptoms and signs. It is inherited in an autosomal recessive manner due to a mutation in the ataxia telangiectasia mutated () gene, which encodes a protein kinase with a domain related to a phosphatidylinositol 3-kinase (PI-3 kinase) proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. The characteristics of the disease include progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctiva, immunodeficiency with frequent infections, and an increased risk for malignancy.

Exome Analysis Identified Novel Homozygous Splice Site Donor Alteration in Gene in a Saudi Family Associated With Spastic Diplegia Cerebral Palsy, Developmental Delay, and Intellectual Disability.

Hereditary spastic paraplegias (HSPs) is a rare heterogeneous group of neurodegenerative diseases, with upper and lower limb spasticity motor neuron disintegration leading to paraplegias. gene (OMIM: 600417) encode a hydrolase enzyme 5'-nucleotidase, cytosolic II play an important role in maintaining the balance of purine nucleotides and free nucleobases in the spinal cord and brain. In this study we have identified a large consanguineous Saudi family segregating a novel homozygous splice site donor alteration in gene leading to spastic diplegia cerebral palsy, developmental delay and microcephaly.

Autosomal recessive cerebellar ataxia with spasticity due to a rare mutation in gene in a large consanguineous Saudi family.

The nonlysosomal glucosylceramidase β2 () gene encode an enzyme that catalyzes the hydrolysis of glucosylceramide to glucose and ceramide. Mutations in the gene have been reported to cause hereditary spastic paraplegia, autosomal recessive cerebellar ataxia with spasticity, and Marinescu-Sjögren-Like Syndrome. In this study, we report the clinical features and genetic diagnosis of autosomal recessive cerebellar ataxia with spasticity due to a rare mutation in gene in a large consanguineous Saudi family.

Novel compound heterozygous mutations in gene leading to developmental delay and Primary Microcephaly in Saudi Family.

Objective: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly.

A novel mutation in gene in a Saudi patient with bilateral facial weakness and scapular winging.

Titin () is a large gene with 363 exons that encodes a large abundant protein (longest known polypeptide in nature) that is expressed in cardiac and skeletal muscles. has an important role in the sarcomere organization, assembly of muscles, transmission of the force at the Z-line, passive myocyte stiffness, and resting tension maintenance in the I-band region. Mutation in extreme C terminus of , situated at the end of M-band of the in chromosome 2q31, results in tibial muscular dystrophy (TMD), also called Udd Distal Myopathy, which is an autosomal dominant distal myopathy.

A very rare form of autosomal dominant progressive myoclonus epilepsy caused by a novel variant in the PRICKLE1 gene.

Purpose: Progressive myoclonus epilepsy (PME) comprises a group of heterogeneous disorders defined by the combination of action myoclonus, epileptic seizures, and progressive neurologic deterioration. Neurologic deterioration may include progressive cognitive decline, ataxia, neuropathy, and myopathy. A number of genes have been identified to cause either isolated PME or diseases that manifest PME.

A novel mutation in gene in a Saudi female with episodic ataxia type 2 with no response to acetazolamide or 4-aminopyridine.

Episodic ataxia is a genetically heterogeneous neurological condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2, caused by calcium voltage-gated channel subunit alpha1 A (CACNA1A MIM: 601011) mutation, is the most common form of episodic ataxia. It is characterized by recurrent attacks of imbalance associated with interictal nystagmus lasting hours to days and triggered by emotional stress or exercise.

Ataxia with ocular apraxia type 2 not responding to 4-aminopyridine: A rare mutation in the gene in a Saudi patient.

Ataxia with ocular apraxia type 2 is an autosomal recessive disorder caused by a mutation in the senataxin () gene. The disease is characterized by early onset cerebellar ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and increased levels of α-fetoprotein. Reported here is a rare homozygous frameshift deletion c.

A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family.

Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome.

A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy.

Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain.