Natural history of SPTBN4-related neurodevelopmental disorder with hypotonia, neuropathy, and deafness.

Background: Pathogenic variants in SPTBN4 have been linked to autosomal recessive "neurodevelopmental disorder with hypotonia, neuropathy, and deafness" (MIM# 617519) known as NEDHND. The disorder is highlighted with neuropathy, muscle weakness, and infrequent appearance of seizures in the affected individuals. This study aims to investigate the natural history of the disease, present genetic and clinical appearance of the syndrome in a highly consanguineous population, Saudi Arabia, and finally provide an overview of the reported cases, their clinical features, and disease-causing variants.

Exome Sequencing Reveals Novel Variants in Saudi Patients with Congenital Titinopathies.

Our goal was to determine the genetic basis of early-onset myopathy in patients from two unrelated families. Whole-exome sequencing, autozygosity mapping, and confirmatory targeted Sanger sequencing were performed using genomic DNA extracted from blood samples from three myopathic patients of two unrelated families. Variant filtering and pathogenicity analyses were evaluated according to standard protocols and up-to-date pipelines applied at the King Faisal Specialist Hospital and Research Center.

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41.

Pyrostigmine therapy in a patient with VAMP1-related congenital myasthenic syndrome.

Congenital myasthenic syndrome comprises several genetic disorders that impair neuromuscular junction transmission. Causative mutations occur in at least 30 genes, approximately 6-8% of which are presynaptic. One such gene, VAMP1, encodes vesicle-associated membrane protein-1, which is crucial in the formation and fusion of synaptic vesicles with the presynaptic membrane at the neuromuscular junction.