Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
Objectives: Patients with epilepsy have a high risk of accidents and injuries, resulting in minimized physical activity and social withdrawal. Therefore, we surveyed the prevalence and the types of injuries that patients with epilepsy may endure, and the factors that may increase the risk of injuries.
Methods:In this cohort study, adult and pediatric patients diagnosed with epilepsy (age ≥ 7 years) and a close family member (parents/guardian) attending the outpatient epilepsy clinics at King Fahd Medical City (Riyadh, Saudi Arabia) were interviewed by neurologists. They reviewed the patients' medical records and administered a structured questionnaire to identify and compare several variables, including injury frequency versus seizure type and seizure frequency, number of antiseizure medications used, medication compliance, and work and social limitations.Results: Out of 200 patients, 86 (43%) sustained injuries during an attack of their habitual seizures. Almost half of this group showed a tendency for recurrent injuries. The most common traumas were soft tissue injury (36.5%), head injury (32%), dental injury (8.5%), burns (7%), dislocation (7%), fractures (6.5%), and submersion (2%). Two-thirds of the patients had their injury at home. 64% of patients who had seizures for more than 10 years sustained multiple injuries (P = .003). Injury frequency was higher among patients with daily or monthly seizures (P = .03). 76% of patients who suffered injuries more than twice had generalised tonic-clonic seizures, and genetic generalised epilepsy was encountered more in injured patients (P = .02). Also, patients on polytherapy were more likely than those on monotherapy to have an injury (P = .003).Significance: Two-fifths of the patients reported seizure-related injuries. The most common were soft-tissue injuries and head traumas, while homes were the most frequent site. In addition, longer epilepsy duration, generalized tonicclonic seizures, and polytherapy were associated with a higher prevalence of injuries. Therefore, injury prevention strategies should be developed for PWE, especially for those at higher risk.
Epilepsy, one of the most prevalent chronic neurological diseases, can cause severe morbidity as well as mortality. A mutation of the
KCNMA1
gene results in a rare genetic disease that causes epilepsy as its core presentation. Both neurological and non-neurological manifestations have been reported in patients with
KCNMA1
gene mutation. We are reporting a
KCNMA1
gene variant referred to as c.2369C>T (p. Pro790Leu), which encodes the subunit of alpha of calcium-sensitive potassium channels, which causes epilepsy but not dyskinesia in a young Saudi female who is the daughter of consanguineous parents. Our case shows that calcium-sensitive potassium channels can cause an isolated generalized epilepsy as reported previously in a single case. Moreover, this case aids in delineating the clinical and structural picture and the treatment of the
KCNMA1
gene mutation in patients.
Objectives: To measure the burden of insomnia and daytime sleepiness (DTS) and their effects on sleep quality, and the risk factors of poor quality of sleep.
Methods:We conducted a cross-sectional study of 218 epilepsy patients. We administered well-validated and previously translated questionnaires to assess sleep quality, insomnia, and DTS using the Pittsburgh
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