Relevance to Autism

A de novo missense variant in the PTDSS1 gene was identified in an ASD proband from a multiplex family (Yuen et al., 2015), while an inherited splice-site variant in this gene was identified in an ASD proband from the iHART cohort (Ruzzo et al., 2019). Gracie et al., 2022 identified a 3-year-old female presenting with developmental delay and a formal diagnosis of autism and a de novo missense variant in the PTDSS1 gene; functional assessment of this variant demonstrated loss of catalytic activity compared to wild-type enzyme. A maternally-inherited multigenic duplication affecting the PTDSS1 gene had previously been identified in a male ASD proband born to non-consanguineous Lebanese parents in Soueid et al., 2016.

Molecular Function

The protein encoded by this gene catalyzes the formation of phosphatidylserine from either phosphatidylcholine or phosphatidylethanolamine. Phosphatidylserine localizes to the mitochondria-associated membrane of the endoplasmic reticulum, where it serves a structural role as well as a signaling role. Heterozygous de novo missense variants in this gene that result in gain-of-function of phosphatidylserine synthase 1 are a cause of Lenz-Majewski hyperostotic dwarfism (OMIM 151050), a rare condition characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial and dental anomalies, loose skin, and distal limb anomalies, particularly brachydactyly and symphalangism (Sousa et al., 2014).

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