Relevance to Autism

Desprez et al., 2025 reported six different missense variants in the DPYSL5 gene (including the previously identified p.Glu41Lys recurrent variant that was experimentally confirmed as a loss-of-function variant in Jeanne et al., 2021) in three male fetuses and six individuals aged up to 10 years old; all living participants in this cohort had developmental delay (6/6), predominantly in language (5/6), and mild to severe intellectual disability (5/5), while four of these individuals had autism spectrum disorder. Subsequent functional assays of novel DPYSL5 missense variants in differentiating mouse or human neuronal cultures in Desprez et al., 2025 revealed impairments in dendritic arborization, axonal elongation, and synaptic density. Of the nine individuals with Ritscher-Schinzel syndrome 4 reported in Jeanne et al., 2021, ASD was reported in one and stereotypic movements were reported in two others. A de novo missense variant in the DPYSL5 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Molecular Function

This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. Heterozygous variants in the DPYSL5 gene are responsible for Ritscher-Schinzel syndrome 4 (OMIM 619435), a disorder characterized by a constellation of congenital anomalies, including dysmorphic craniofacial features and structural brain anomalies, associated with global developmental delay and impaired intellectual development (Jeanne et al., 2021).

External Links

References