{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:42Z","timestamp":1753892082114,"version":"3.41.2"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Science and Technology Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The serine active site-containing protein 1 (<jats:italic>SERAC1<\/jats:italic>) biallelic variant usually causes MEGDEL syndrome, clinically characterized by increased excretion of 3-methylglutaconic in the urine, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain MRI scans. In this study, we present a case from a Chinese family with disordered metabolism and dystonia owing to <jats:italic>SERAC1<\/jats:italic> variants; the clinical phenotypes of the proband were different from those of MEGDEL syndrome but were similar to those juvenile-onset complicated hereditary spastic paraplegia. Thus, in this study, we aimed to confirm the relationship between <jats:italic>SERAC1<\/jats:italic> variants and complicated hereditary spastic paraplegia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MRI and laboratory tests, including gas chromatography\/mass spectrometry (GC\/MS), were carried out for the proband. Whole-exome sequencing was used to detect the candidate <jats:italic>SERAC1<\/jats:italic> variants. Variants were verified using Sanger sequencing. Various software programs (PolyPhen-2, MutationTaster, PROVEAN, and SIFT) were used to predict the pathogenicity of novel variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain MRI scans showed a symmetric flake abnormal signal shadow in the bilateral basal ganglia in T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) analyses. The excretion of 3-methylglutaconic acid was found to be increased in our GC\/MS analysis. Whole-exome sequencing showed novel compound heterozygous variants, including a novel c.1495A&amp;gt;G (p.Met499Val) variant in exon 14 of <jats:italic>SERAC1<\/jats:italic> inherited from the father and a novel c.721_722delAG (p.Leu242fs) variant in exon 8 inherited from the mother. The pathogenicity prediction results showed that these two variants were deleterious.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study presented a patient with complicated hereditary spastic paraplegia caused by <jats:italic>SERAC1<\/jats:italic> variants. These findings expand the number of known <jats:italic>SERAC1<\/jats:italic> variants and the phenotypic spectrum associated with SERAC1 deficiency. This study may contribute to counseling and prevention of hereditary diseases through prenatal.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2021.816265","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T05:49:13Z","timestamp":1644558553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese 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