{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:29:46Z","timestamp":1790105386390,"version":"4.0.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Asparagine synthetase deficiency (ASNSD; OMIM# 615574) is a severe autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in <jats:italic>ASNS<\/jats:italic> (OMIM# 108370). Clinical features of ASNSD include congenital microcephaly, profound psychomotor impairment, progressive encephalopathy, refractory epilepsy, and characteristic neuroimaging abnormalities. Since its initial description, approximately 100 cases have been documented worldwide with 60 distinct <jats:italic>ASNS<\/jats:italic> variants reported. Here, we report a Chinese patient with prenatal microcephaly, intrauterine growth retardation (IUGR) and reduced middle cerebral artery blood flow velocity. Postnatally, she presented with progressive microcephaly, profound psychomotor delay and intractable epilepsy. Brain MRI showed corpus callosum hypoplasia, cerebellar hypoplasia, delayed myelination, cortical atrophy, enlarged ventricles and gyral simplification. Whole-exome sequencing (WES) was applied to detect the causative variants and identified a novel homozygous variant c.4\u202fT\u202f&amp;gt;\u202fG (p.Cys2Gly), in <jats:italic>ASNS<\/jats:italic> in our patient that was inherited from the heterozygous unaffected parents. Our report contributes to the expanding genotypic and prenatal phenotype spectrum of ASNSD.<\/jats:p>","DOI":"10.3389\/fnins.2025.1570160","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T06:07:28Z","timestamp":1747030048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy"],"prefix":"10.3389","volume":"19","author":[{"given":"Shuangxi","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhen","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1002\/humu.24101","article-title":"Rapid exome sequencing and adjunct RNA studies confirm the pathogenicity of a novel homozygous ASNS splicing variant in a critically ill neonate","volume":"41","author":"Akesson","year":"2020","journal-title":"Hum. 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