{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:02:51Z","timestamp":1784203371313,"version":"3.55.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Congenital disorders of glycosylation (CDG) are a group of multi-systemic genetic disorders. Over 100 monogenic human diseases were known related with defects in glycosylation process. Defects of\n                      <jats:italic>SSR4<\/jats:italic>\n                      gene lead to a rare X linked pattern of CDG which has been rarely reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We reported a Chinese boy with developmental delay, microcephaly, and epileptic seizures. Whole exome sequencing and Sanger sequencing were performed in the family.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      A novel maternal splice variant c.351+1del in\n                      <jats:italic>SSR4<\/jats:italic>\n                      gene was identified by trio-exome sequencing, and confirmed by Sanger sequencing. The functional effect of the variant was further investigated by minigene. The minigene results showed three abnormal splice forms: (1) 1\u2005bp deletion in 3\u2032 end of exon 4; (2) 42\u2005bp deletion in 3\u2032 end of exon 4; (3) skipping of exon 4. All three forms resulted in truncated proteins. c.351+1del in\n                      <jats:italic>SSR4<\/jats:italic>\n                      gene causes congenital disorder of glycosylation, type Iy, consisted with the proband's phenotype. Up to date, all of the pathogenic\n                      <jats:italic>SSR4<\/jats:italic>\n                      gene variants were null variants. The most variants were reported in exon 4. Patients (within or between families) carrying the same variants exhibited phenotypic heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The current study expanded the pathogenic variant spectrum of\n                      <jats:italic>SSR4<\/jats:italic>\n                      gene and revealed the impact of c.351+1del on\n                      <jats:italic>SSR4<\/jats:italic>\n                      splicing. Standardizing the transcript and naming conventions of variants were crucial for the study of\n                      <jats:italic>SSR4<\/jats:italic>\n                      genotypes and phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2025.1651524","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:27:02Z","timestamp":1761283622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel SSR4 gene splice variant leads to congenital disorder of glycosylation, type 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