{"i":"NRXN3","#text":"Case Report-An Inherited Loss-of-FunctionVariant Potentially Causes a Neurodevelopmental Disorder with Autism Consistent with Previously Described 14q24.3-31.1 Deletions."}

Researchers found a genetic change in the NRXN3 gene in a 5-year-old girl with autism, developmental delays, and behavioral challenges. She inherited this genetic change from her mother, who doesn't have any symptoms. This suggests that having this genetic change doesn't always cause problems. This is the first detailed report showing that changes in this specific gene can cause autism-like symptoms.

This case report describes a 5-year-old girl with autism spectrum disorder, developmental delay, and behavioral issues who carried an inherited loss-of-function variant in the NRXN3 gene. The variant was inherited from her unaffected mother, suggesting incomplete penetrance. NRXN3 encodes neurexin-3, a protein important for neuronal cell recognition and signaling. This represents the first detailed report of a specific loss-of-function variant in NRXN3 causing a neurodevelopmental phenotype identical to that seen with larger chromosomal deletions in the same region, confirming NRXN3 as a candidate gene for neurodevelopmental disorders with autism.

This case confirms NRXN3 as a candidate gene for autism spectrum disorders. The incomplete penetrance observed suggests complex inheritance patterns that are important for genetic counseling. Further research is needed to establish the full spectrum of NRXN3-related phenotypes.

Single case report limits generalizability. Small sample size prevents assessment of variant frequency or penetrance rates. Functional studies of the variant were not performed. Long-term outcomes not assessed.

Heterozygous, large-scale deletions at 14q24.3-31.1 affecting the neurexin-3 gene have been associated with neurodevelopmental disorders such as autism. Both "de novo" occurrences and inheritance from a healthy parent suggest incomplete penetrance and expressivity, especially in autism spectrum disorder.encodes neurexin-3, a neuronal cell surface protein involved in cell recognition and adhesion, as well as mediating intracellular signaling.is expressed in two distinct isoforms (alpha and beta) generated by alternative promoters and splicing. MM/Results: Using exome sequencing, we identified a monoallelic frameshift variant c.159_160del (p.Gln54AlafsTer50) in thebeta isoform (NM_001272020.2) in a 5-year-old girl with developmental delay, autism spectrum disorder, and behavioral issues. This variant was inherited from her mother, who did not have any medical complaints.

This is the first detailed report of a loss-of-function variant incausing an identical phenotype, as reported for heterozygous large-scale deletions in the same genomic region, thereby confirmingas a novel gene for neurodevelopmental disorders with autism.