Relevance to Autism

A nonsense variant in the GLI3 gene was identified in an individual from the Children's Neurodevelopmental Center, Hasbro Children's Hospital who was diagnosed with ASD and presented with dysmorphic features, sensorineural hearing loss, postaxial polydactyly of the hands and feet, right hydronephrosis, global developmental delay, aggression, self-injurious behavior, sensory processing disorder, anxiety, ADHD, and motor stereotypies (Lob et al., 2024). Siracusano et al., 2019 had previously described a 7-year-old Italian male with Greig cephalopolysyndactyly syndrome and a comorbid diagnosis of autism spectrum disorder who had inherited a frameshift variant in the GLI3 gene from his father, who also had Greig cephalopolysyndactyly syndrome and presented with subclinical autistic symptoms. Two de novo missense variants and a de novo coding-synonymous variant in this gene have also been identified in ASD probands from the Autism Sequencing Consortium and the Simons Simplex Collection (De Rubeis et al., 2014; Iossifov et al., 2014; Satterstrom et al., 2020).

Molecular Function

This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B.

External Links

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