AUTHOR=Sun Wenqiang , Jin Xinyun , Zhu Xueping 

TITLE=A novel SSR4 variant associated with congenital disorder of glycosylation: a case report and related analysis

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1402883

DOI=10.3389/fgene.2024.1402883

ISSN=1664-8021

ABSTRACT=<sec><title>Introduction</title><p>Congenital disorders of glycosylation (CDG) refer to monogenetic diseases characterized by defective glycosylation of proteins or lipids causing multi-organ disorders. Here, we investigate the clinical features and genetic variants of <italic>SSR4</italic>-CDG and conduct a preliminary investigation of its pathogenesis.</p></sec><sec><title>Methods</title><p>We retrospectively report the clinical data of a male infant with early life respiratory distress, congenital diaphragmatic eventration, cosmetic deformities, and moderate growth retardation. Peripheral blood was collected from the case and parents, genomic DNA was extracted and whole-exome sequencing was performed. The mRNA expression of <italic>SSR4</italic> gene was quantified by Real-time Quantitative PCR. RNA sequencing analysis was subsequently performed on the case and a healthy child.</p></sec><sec><title>Results</title><p>Whole-exome sequencing of the case and his parents’ genomic DNA identified a hemizygous c.80_96del in <italic>SSR4</italic>, combined with the case’s clinical features, the diagnosis of CDG was finally considered. In this case, the expression of <italic>SSR4</italic> was downregulated. The case were present with 1,078 genes downregulated and 536 genes upregulated. <italic>SSR4</italic> gene expression was significantly downregulated in the case. Meanwhile, gene set enrichment analysis (GSEA) revealed that <italic>SSR4</italic>-CDG may affect hemostasis, coagulation, catabolism, erythrocyte development and homeostatic regulation, and muscle contraction and regulation, etc. Improvement of growth retardation in case after high calorie formula feeding and rehabilitation training.</p></sec><sec><title>Conclusion</title><p>Our study expanded the <italic>SSR4</italic>-CDG variant spectrum and clinical phenotype and analyzed pathways potentially affected by <italic>SSR4</italic>-CDG, which may provide further insights into the function of <italic>SSR4</italic> and help clinicians better understand this disorder.</p></sec>