No abstract

Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic.

Background: There is a large gap between the needs of individuals diagnosed with autism spectrum disorder (ASD) and the currently available services in Saudi Arabia. Services are often difficult to access, inconsistent in quality, incomplete, unsatisfactory, and costly. As such, there is a national need for expert consensus on the appropriate standards for the assessment and management of children on the autism spectrum. Methodology: A guideline development group (GDC) was formed by professionals representing all related specialties and institutions involved in the management of individuals on the autism spectrum in Saudi Arabia. They met on a regular basis over 21 months. The guideline development process consisted of five steps starting from reviewing existing guidelines and ending with discussing and writing this manuscript. A formal voting process was utilized and recommendations were discussed until a consensus was reached. Results: There was consensus on the following: A specialized diagnostic assessment needs to be carried out by an experienced multidisciplinary team for children referred to assess for ASD. They should be assessed for medical etiology, their behavioral history carefully reviewed, and symptoms directly observed. Longitudinal assessments are encouraged to reflect the effects of symptoms on the individual’s ability to function while with their family, among peers, and in school settings. An additional formal assessment of language, cognitive, and adaptive abilities as well as sensory status is essential to complete the diagnostic process. Interventions should be individualized, developmentally appropriate, and intensive, with performance data relevant to intervention goals to evaluate and adjust interventions. Target symptoms must be identified to address and develop monitoring systems to track change. Conclusion: ASD is a complex condition with widely varying clinical manifestations, thus requiring evaluation and intervention by a range of professionals working in coordination. Behavioral and environmental interventions are the key to optimal outcomes, in conjunction with medications when indicated for specific symptoms. Parental involvement in interventions is vital to sustaining therapeutic gains.

Even in the era of information “prosperity” in the form of databases and registries that compile a wealth of data, information about ASD and ADHD remains scattered and disconnected. These data systems are powerful tools that can inform decision-making and policy creation, as well as advancing and disseminating knowledge. Here, we review three types of data systems (patient registries, clinical trial registries and genetic databases) that are concerned with ASD or ADHD and discuss their features, advantages and limitations. We noticed the lack of ethnic diversity in the data, as the majority of their content is curated from European and (to a lesser extent) Asian populations. Acutely aware of this knowledge gap, we introduce here the framework of the Neurodevelopmental Disorders Database (NDDB). This registry was designed to serve as a model for the national repository for collecting data from Saudi Arabia on neurodevelopmental disorders, particularly ASD and ADHD, across diverse domains.