Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy
Asparagine synthetase deficiency (ASNSD; OMIM# 615574) is a severe autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in ASNS (OMIM# 108370). Clinical features of ASNSD include congenital microcephaly, profound psychomotor impairment, progressive encephalopathy,...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1570160/full |
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| author | Shuangxi Cheng Fang Zhang Qingming Wang Jianfei Zhang Guizhen Lyu Yanwei Li Xinlong Zhou Haiming Yuan |
| author_facet | Shuangxi Cheng Fang Zhang Qingming Wang Jianfei Zhang Guizhen Lyu Yanwei Li Xinlong Zhou Haiming Yuan |
| author_sort | Shuangxi Cheng |
| collection | DOAJ |
| description | Asparagine synthetase deficiency (ASNSD; OMIM# 615574) is a severe autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in ASNS (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 ASNS 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 T > G (p.Cys2Gly), in ASNS in our patient that was inherited from the heterozygous unaffected parents. Our report contributes to the expanding genotypic and prenatal phenotype spectrum of ASNSD. |
| format | Article |
| id | doaj-art-e9bb9e3df4264ef0bc1caefca6edd8a1 |
| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-e9bb9e3df4264ef0bc1caefca6edd8a12025-08-20T02:15:37ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-05-011910.3389/fnins.2025.15701601570160Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsyShuangxi Cheng0Fang Zhang1Qingming Wang2Jianfei Zhang3Guizhen Lyu4Yanwei Li5Xinlong Zhou6Haiming Yuan7Dongguan Maternal and Child Health Care Hospital, Dongguan, ChinaDongguan Maternal and Child Health Care Hospital, Dongguan, ChinaDongguan Maternal and Child Health Care Hospital, Dongguan, ChinaDongguan Maternal and Child Health Care Hospital, Dongguan, ChinaDongguan Labway Clinical Laboratory Co., Ltd., Dongguan, ChinaDongguan Labway Clinical Laboratory Co., Ltd., Dongguan, ChinaDongguan Maternal and Child Health Care Hospital, Dongguan, ChinaDongguan Maternal and Child Health Care Hospital, Dongguan, ChinaAsparagine synthetase deficiency (ASNSD; OMIM# 615574) is a severe autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in ASNS (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 ASNS 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 T > G (p.Cys2Gly), in ASNS in our patient that was inherited from the heterozygous unaffected parents. Our report contributes to the expanding genotypic and prenatal phenotype spectrum of ASNSD.https://www.frontiersin.org/articles/10.3389/fnins.2025.1570160/fullASNSmicrocephalypsychomotor delayepilepsybrain anomalies |
| spellingShingle | Shuangxi Cheng Fang Zhang Qingming Wang Jianfei Zhang Guizhen Lyu Yanwei Li Xinlong Zhou Haiming Yuan Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy Frontiers in Neuroscience ASNS microcephaly psychomotor delay epilepsy brain anomalies |
| title | Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy |
| title_full | Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy |
| title_fullStr | Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy |
| title_full_unstemmed | Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy |
| title_short | Case Report: a novel homozygous ASNS variant in a Chinese female with severe microcephaly, encephalopathy and epilepsy |
| title_sort | case report a novel homozygous asns variant in a chinese female with severe microcephaly encephalopathy and epilepsy |
| topic | ASNS microcephaly psychomotor delay epilepsy brain anomalies |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1570160/full |
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