2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A Homozygous Novel Pathogenic Variant in SYNJ1 and its Clinical Presentation

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This study focuses on the identification and characterization of a novel homozygous SYNJ1 variant that causes developmental and epileptic encephalopathy. The researchers performed exome sequencing and identified a homozygous SYNJ1 NM_003895.3 c.242-2A>G variant in an affected individual. This variant is associated with global developmental delay (GDD), seizures, dystonia, and encephalopathy.<br /><br />SYNJ1 is a gene that plays a dual function as a phosphatidyl-inositol phosphatase, which is essential for neurotransmitter vesicle turnover, as well as a regulator of the actin cytoskeleton. The researchers found that affected individuals with the homozygous SYNJ1 variant exhibited poor feeding, Parkinsonism, L-Dopa response, tremor, seizure, hypotonia, and hypertonia. Other features observed in these individuals include scoliosis, apparent microcephaly, and hypertelorism.<br /><br />The study also provides information on the genotype-phenotype correlation of SYNJ1-associated conditions. Biallelic loss-of-function variants in SYNJ1 were found to be associated with profound intellectual disability, scoliosis, myopathy, opisthotonus, and severe illness. In contrast, biallelic loss-of-function missense variants were associated with developmental and epileptic encephalopathy.<br /><br />Early-onset Parkinsonism was observed in individuals with various allele combinations of SYNJ1, including at least one missense variant. Symptoms of Parkinsonism included bradykinesia, dysarthria, and limited eye movements.<br /><br />In conclusion, this study identifies and characterizes a novel homozygous SYNJ1 variant associated with developmental and epileptic encephalopathy. It also provides insights into the different phenotypic manifestations associated with loss-of-function and missense variants in SYNJ1. The findings contribute to the understanding of SYNJ1-related disorders and highlight the importance of this gene in neurodevelopment and neurotransmission.

Asset Subtitle

Presenting Author - Christie Taylor, BS; Co-Author - Mary Maj, PhD; Co-Author - Kevin S. Landau, MD; Co-Author - Dong Li, PhD; Co-Author - Elizabeth J. Bhoj, MD, PhD; Co-Author - Helga V. Toriello, MS, PhD; Co-Author - Beverly Nelson, MD; Co-Author - Sarah Gluschitz, MSc; Co-Author - Ruth H. Walker, MD, PhD; Co-Author - Andrew K. Sobering, PhD;

Meta Tag

Cognitive Disorders

Congenital Anomaly

Exome sequencing

Genetic Testing

Genotype-Phenotype Correlations

Intellectual disability

Co-Author Mary Maj, PhD

Co-Author Kevin S. Landau, MD

Co-Author Dong Li, PhD

Co-Author Elizabeth J. Bhoj, MD, PhD

Co-Author Helga V. Toriello, MS, PhD

Co-Author Beverly Nelson, MD

Co-Author Sarah Gluschitz, MSc

Co-Author Ruth H. Walker, MD, PhD

Co-Author Andrew K. Sobering, PhD

Presenting Author Christie Taylor, BS

Keywords

SYNJ1 variant

developmental and epileptic encephalopathy

exome sequencing

global developmental delay

seizures

dystonia

encephalopathy

phosphatidyl-inositol phosphatase

actin cytoskeleton

Parkinsonism