Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients

Abstract

Developmental regression describes a child who begins to lose his previously acquired milestones skills after he has reached a certain developmental stage and though affects his childhood development. It is associated with neurodegenerative diseases including leukodystrophy and neuronal ceroid lipofuscinosis diseases (NCLs), one of the most frequent childhood-onset neurodegenerative disorders. The current study focused on screening causative genes of developmental regression diseases comprising neurodegenerative disorders in Egyptian patients using next-generation sequencing (NGS)-based analyses as well as developing checklist to support clinicians who are not familiar with these diseases. A total of 763 Egyptian children (1 to 11 years), mainly diagnosed with developmental regression, seizures, or visual impairment, were studied using whole exome sequencing (WES). Among 763 Egyptian children, 726 cases were early clinically and molecularly diagnosed, including 482 cases that had pediatric stroke, congenital infection, and hepatic encephalopathy; meanwhile, 192 had clearly dysmorphic features, 31 showed central nervous system (CNS) malformation, 17 were diagnosed by leukodystrophy, 2 had ataxia telangiectasia, and 2 were diagnosed with tuberous sclerosis. The remained 37 out of 763 candidates were suspected with NCLs symptoms; however, 28 were confirmed to be NCLs patients, 1 was Kaya-Barakat-Masson syndrome, 1 was diagnosed as infantile neuroaxonal dystrophy, and 7 cases required further molecular diagnosis. This study provided an NGS-based approach of the genetic causes of developmental regression and neurodegenerative diseases as it comprised different variants and de novo mutations with complex phenotypes of these diseases which in turn help in early diagnoses and counseling for affected families.

Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

“…More recently, Olfe et al have demonstrated CTLA-4 insufficiency due to a novel CTLA-4 deletion using ClinCNV ( German and Stephan, 2019 ; Olfe et al, 2023 ), further highlighting the synergy of CNV calling with WES analysis. Beyond the scope of autoimmune diseases, NGS techniques have also been extensively utilized in identifying causal variants (including CNVs) contributing to cancer ( van Dijk et al, 2014 ; Papp et al, 2021 ; Satam et al, 2023 ), congenital ( Lai et al, 2021 ; Li et al, 2022 ; Liu et al, 2022 ; Wang et al, 2022 ; Wu et al, 2022 ; Refeat et al, 2023 ), cardiovascular ( Hu et al, 2023 ) and hematological diseases ( Hassan et al, 2023 ).…”