Identifying the Potential Role of Missense KIRREL3 Variants in Neurodevelopmental Phenotypes: A Case Series

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• Neurodevelopmental disorders are often linked to genetic variations.
• The KIRREL3 gene is expressed in key brain regions like the basal ganglia and amygdala and has been previously associated with neurodevelopmental disorders.

Purpose of the Study:

• To investigate the role of rare missense variants in the KIRREL3 gene in individuals with neurodevelopmental disorders.
• To identify novel KIRREL3 variants and assess their potential impact on neurodevelopment.

Main Methods:

• Utilized GeneMatcher and the Simons Foundation Powering Autism Research (SPARK) project to identify individuals with KIRREL3 variants.
• Analyzed 26 individuals with rare missense variants in KIRREL3, predicted to be damaging by REVEL scores.
• Conducted a literature review to identify previously reported KIRREL3 variants in affected individuals.

Main Results:

• Identified 26 individuals with diverse rare missense variants in KIRREL3, all diagnosed with neurodevelopmental conditions.
• These diagnoses included autism spectrum disorder, global developmental delay, intellectual disability, and learning disability.
• Found 10 additional rare KIRREL3 missense variants in 13 individuals with autism spectrum disorder or intellectual disability from previous studies.

Conclusions:

• Rare missense variants in KIRREL3 are potentially implicated in a spectrum of neurodevelopmental disorders.
• Further research is warranted to fully understand the contribution of KIRREL3 variants to neurodevelopmental conditions.