First Report from Saudi Arabia of Trimethylaminuria Caused by a Premature Stop Codon Mutation in the Gene.

Background: Trimethylaminuria (TMAU) is a rare recessive genetic disorder with limited global prevalence. To date, there have been no official reports of TMAU cases documented in Saudi Arabia.

Purpose: In this study, we developed a liquid chromatography-mass spectrometry (LC-MS) method for the analysis of trimethylamine (TMA) and Trimethylamine N-Oxide (TMAO) in urine and plasma samples for the first reported case of TMAU in Saudi Arabia.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

A nationwide cross-sectional study in Saudi Arabia for the assessment of understanding and practices of clinicians towards personalized genetic testing.

In order to plan and facilitate the culture of personalized / precision medicine in medical practices within any healthcare institution, it is requisite for healthcare professionals like clinicians to have a clear understanding and approach towards the practices of personalized genetic testing. This nationwide cross-sectional study aimed to measure the perceptions and knowledge of clinicians towards personalized genetic testing and assess their current practices of personalized genetic testing in clinical settings through an online self-administered questionnaire in Saudi Arabia. The results of the study revealed that almost two-fifths of participants were responsible for ordering genetic tests directly (39.

Ocular mucoadhesive and biodegradable spanlastics loaded cationic spongy insert for enhancing and sustaining the anti-inflammatory effect of prednisolone Na phosphate; Preparation, I-optimal optimization, and In-vivo evaluation.

This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses.

Experts' Opinion in Fabry Disease Management and the Unmet Medical Need: The Saudi Perspective.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations. Its global incidence ranges from 1:40,000 to 1:170,000. This expert review evaluates the available guidelines, the status of diagnosed but untreated patients with FD, and the challenges in diagnosing and managing FD in the Kingdom of Saudi Arabia (KSA).

Nanofiber-Based Drug Delivery Systems: A Review on Its Applications, Challenges, and Envisioning Future Perspectives.

Nanomaterials, especially nanofibers, hold considerable promise as drug delivery systems (DDS) by providing targeted administration of drugs due to their unique properties, such as large surface area, high porosity, and mechanical robustness. Nanofibers can be fabricated using various techniques like electrospinning, self-assembly, phase separation, and template synthesis, offering properties such as adjustable size, shape, high precision, and biodegradability. Additionally, features such as multiple target functionalization, controlled release of the drug, and prolonged circulation of the drug make nanofibers particularly suitable for biomedical applications, including drug delivery, tissue regeneration, and biosensing.

Biallelic loss-of-function variant causes intellectual disability, developmental delay, and dysmorphic features.

Background: HMGXB4 (additionally known as HMG2L1) is a non-histone DNA-binding protein that contains a single HMG-box domain. HMGXB4 was originally described in Xenopus where it was seen to negatively regulate the Wnt/β-catenin signaling pathway.

Materials And Methods: In this study, we conducted a genetic and clinical evaluation of a single family with three affected individuals suffering from intellectual disability (ID), global developmental delay (GDD) and dysmorphic facial features.

Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder.

Background: Neuron navigator 3 (NAV3) is characterized as one of the neuron navigator family (NAV1, NAV2, NAV3) proteins predominantly expressed in the nervous system. The NAV3-encoded protein comprises a conserved AAA and coiled-coil domains characteristic of ATPases, which are associated with different cellular activities.

Methods: We describe a Saudi proband presenting a complex recessive neurodevelopmental disorder (NDD).

A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9).

Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms are caused by disease-causing variants in several genes, including GLI1, GLI3, ZNF141, FAM92A, IQCE, KIAA0825, MIPOL1, STKLD1, PITX1, and DACH1. Whole exome sequencing (WES) followed by bi-directional Sanger sequencing was performed for the single affected individual (II-1) of the family to reveal the disease causative variant/gene.

Genetic Microcephaly in a Saudi Population: Unique Spectrum of Affected Genes Including a Novel One.

Genetic microcephaly is linked to an increased risk of developmental disabilities, epilepsy, and motor impairment. The aim of this study is to describe the spectrum of identifiable genetic etiologies, clinical characteristics, and radiologic features of genetic microcephaly in patients referred to a tertiary center in Saudi Arabia. This is a retrospective chart review study of all patients with identifiable genetic microcephaly presenting to a tertiary center in Saudi Arabia.

Clinical and Molecular Characteristics of Neuronal Ceroid Lipofuscinosis in Saudi Arabia.

Background: Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population.

Methods: A retrospective review of electronic medical records was conducted for 63 patients with NCL (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 and 2022.

Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer's disease.

Background: Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer's disease (AD). Numerous studies have asserted a close association between neuroinflammation and disrupted cerebral energetics. During AD progression and other neurodegenerative disorders, a persistent state of chronic neuroinflammation reportedly exacerbates cytotoxicity and potentiates neuronal death.

Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

Background: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment.

Methods: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity.

Phenotype and genotype of 15 Saudi patients with achromatopsia: A case series.

Purpose: Achromatopsia is a rare stationary retinal disorder that primarily affects the cone photoreceptors. Individuals with achromatopsia present with photophobia, nystagmus, reduced visual acuity (VA), and color blindness. Multiple genes responsible for achromatopsia have been identified (e.

Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.

Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present.

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1.