2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Phenotypic Insights into Newly Established Moderate Effect Genes for Autism Spectrum Disorder

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The study focuses on five novel moderate effect genes (HNRNPUL2, ITSN1, MARK2, NAV3, SCAF1) for autism, identified through the SPARK research cohort of individuals with autism. The study examines the phenotypic information on individuals with loss of function (LoF) variants in these genes and compares it to individuals without genetic findings related to their autism and individuals with LoF variants in well-established autism genes.<br /><br />The results show that individuals with LoF variants in the novel genes were more likely to report intellectual disability compared to individuals with no identifiable genetic result related to their autism. On the other hand, they were less likely to report speech delays or language disorders, motor delay, growth conditions, and visual or auditory conditions. The novel genes also had a higher proportion of transmitted variants compared to well-established autism genes.<br /><br />The study also compared the phenotypes of transmitting parents of the novel genes to sequenced parents in SPARK. The transmitting parents reported a similar percentage of neuropsychiatric symptoms compared to parents with no identifiable genetic results. They were less likely to report anxiety but more likely to report schizophrenia.<br /><br />Additionally, the study assessed individuals in the UK Biobank with LoF variants in the novel genes and found that neuropsychiatric conditions were reported less frequently compared to parents in SPARK. However, this may be due to differences in data collection.<br /><br />In conclusion, the phenotypic data for individuals with variants in the novel genes aligns with these genes having a moderate effect. However, more data is needed to further understand the phenotypic profiles of these genes. The study acknowledges the limitations of the small sample size and emphasizes the need for further research.

Asset Subtitle

Presenting Author - Sarah D. Barns, MPH; Co-Author - Chang K. Shu, PhD; Co-Author - Jessica R. Wright, PhD; Co-Author - Alexandra Goler, BS; Co-Author - Jacob B. Hall, PhD; Co-Author - Bing Han, MS; Co-Author - Irina Astrovskaya, PhD; Co-Author - The SPARK Consortium, -; Co-Author - Natalia Volfovsky, PhD; Co-Author - Yufeng K. Shen, PhD; Co-Author - Pamela Feliciano, PhD; Co-Author - Wendy K. Chung, MD PhD;

Meta Tag

Brain/Nervous System

Clinical History

Cognitive Disorders

Exome sequencing

Genome sequencing

Intellectual disability

Neuroscience

Phenotype

Sequencing

Co-Author Chang K. Shu, PhD

Co-Author Jessica R. Wright, PhD

Co-Author Alexandra Goler, BS

Co-Author Jacob B. Hall, PhD

Co-Author Bing Han, MS

Co-Author Irina Astrovskaya, PhD

Co-Author The SPARK Consortium, -

Co-Author Natalia Volfovsky, PhD

Co-Author Yufeng K. Shen, PhD

Co-Author Pamela Feliciano, PhD

Co-Author Wendy K. Chung, MD PhD

Presenting Author Sarah D. Barns, MPH

Keywords

novel genes

autism

SPARK research cohort

intellectual disability

speech delays

transmitted variants

well-established autism genes

neuropsychiatric symptoms

UK Biobank

phenotypic profiles