ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 13 - 2025 | doi: 10.3389/fped.2025.1651524
This article is part of the Research TopicGenetics and Mechanisms of Neurodevelopmental DisordersView all 10 articles
Novel SSR4 gene splice variant leads to Congenital disorder of glycosylation, type Iy
Provisionally accepted- 1Liuyang People's Hospital, Changsha, China
- 2Third Xiangya Hospital of Central South University, Changsha, China
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Abstract Background: 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 SSR4 gene lead to a rare X linked pattern of CDG which has been rarely reported. Method: We reported a Chinese boy with developmental delay, microcephaly, and epileptic seizures. Whole exome sequencing and Sanger sequencing were performed in the family. Result: A novel maternal splice variant c.351+1del in SSR4 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) 1bp deletion in 3' end of exon 4; 2) 42bp deletion in 3' end of exon 4;3) skipping of exon 4. All three forms resulted in truncated proteins. c.351+1del in SSR4 gene causes congenital disorder of glycosylation, type Iy, consisted with the proband's phenotype. Up to date, all of the pathogenic SSR4 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. Conclusion: The current study expanded the pathogenic variant spectrum of SSR4 gene and revealed the impact of c.351+1del on SSR4 splicing. Standardizing the transcript and naming conventions of variants were crucial for the study of SSR4 genotypes and phenotypes.
Keywords: SSR4, Congenital disorder of glycosylation, whole exome sequencing, Minigene, Transcript
Received: 21 Jun 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chen Chen, alleycc@csu.edu.cn
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