{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:48:42Z","timestamp":1789440522847,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006016","name":"College of Medicine, King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and\/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.<\/jats:p><jats:p><jats:bold>Results and Discussion:<\/jats:bold> Two homozygous variants in <jats:italic>ABHD16A<\/jats:italic> segregated with the disease in the two studied families. <jats:italic>ABHD16A<\/jats:italic> encodes the main brain phosphatidylserine hydrolase. <jats:italic>In vitro<\/jats:italic>, we confirmed that <jats:italic>ABHD16A<\/jats:italic> loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold><jats:italic>ABHD16A<\/jats:italic> loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.<\/jats:p>","DOI":"10.3389\/fneur.2021.720201","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T13:58:23Z","timestamp":1629467903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Pathogenic Variants in ABHD16A Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia"],"prefix":"10.3389","volume":"12","author":[{"given":"Ashraf","family":"Yahia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liena E. 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