Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

Neurodevelopmental Disorders (NDDs) are a group of disorders that typically manifest early in development and may give rise to impaired cognition, communication, adaptive behavior, and psychomotor skills. This study aims to take a more comprehensive view into the genomic landscape of structural variants implicated in NDDs with intellectual disability (ID). We have evaluated the genome of families with a genetically unsolved severe NDD via optical genome mapping. This study identified likely pathogenic or pathogenic structural variants in known NDD genes, including BCL11A, OPHN1, PHF8, SON, and NFIA. Data is available in VCF format, following the standard filtering settings in Bionano Access and available as "variants_combine_filters_inMoleRefine1.vcf" files.

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Case-Control
  • Cohort
  • Family
  • Mendelian
  • Parent-Offspring Trios
• Total number of consented subjects: 52
• Subject Sample Telemetry Report (SSTR)

• BioProject
• MeSH
• Gene

Individuals with a NDD and intellectual disability (ID) and their unaffected family members were included. All affected individuals have ID, in addition to other features of abnormal neurodevelopment such as developmental delay, hypotonia and microcephaly. Despite extensive clinical and standard genetic investigations, a definitive diagnosis for the participants remains unknown. Affected individuals were clinically evaluated by a child neurologist and a general medical practitioner for the study. In addition, previous hospital records were taken into account for evaluation. In relevant cases, magnetic resonance imaging (MRI) scans and computerized tomography (CT) scans were also obtained. A description of developmental milestones was used and the severity of ID was assessed.

• Primary Phenotype: Neurodevelopmental Disorders
• Intellectual Disability

• BCL11A
• NFIA
• OPHN1
• PHF8
• SON

• Principal Investigator
  • Isabelle Schrauwen. Columbia University, New York, NY, USA.
• Co-Investigator
  • Irma Järvelä. University of Helsinki, Helsinki, Finland.