BRIEF RESEARCH REPORT article
Front. Genet.
Sec. Statistical Genetics and Methodology
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1515260
A Novel Missense Variant of HS6ST2 Gene in Paganini-Miozzo Syndrome with a Rare Neurodevelopmental and Endocrine Phenotypes
Provisionally accepted
- 1Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Beijing Genomics Institute (BGI), Shenzhen, China
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Paganini-Miozzo syndrome (MRXSPM) is a globally rare disease caused by hemizygous mutations in the HS6ST2 gene on chromosome Xq26. This study presents the first case of MRXSPM in China, meanwhile the fourth case worldwide. The proband was admitted to the hospital due to developmental delay. Whole exome sequencing (WES) revealed a novel variant, c.764C>A (p.Pro255Glu) missense mutation in the HS6ST2 gene. Brain MRI showed mild lateral ventricular enlargement, and electroencephalogram showed diffuse spikes and waves. Biochemical tests indicated significantly elevated transaminases, blood lactate values, and lactate/pyruvate values. Bioinformatics predictions suggest that this mutation may affect the thermal stability of the HS6ST2 protein. The amino acid where the mutation c.764C>A p.P255Q occurs is conserved across multiple species, specifically being proline in 13 species. In vitro cell experiments demonstrated that this mutant can impact the expression of HS6ST2 protein at 2 post-transcriptional level. Comparison with previously reported cases revealed that different mutations might lead to different alternations in the function of HS6ST2 protein, resulting in distinct clinical phenotypes.
Keywords: Paganini-Miozzo syndrome (MRXSPM), HS6ST2, Whole exome sequencing (WES), developmental delay, Endocrine abnormality
Received: 11 Dec 2024; Accepted: 30 May 2025.
Copyright: © 2025 Zhang, Chang, Du, Cai, Chen and Zhang. 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: Fucheng Cai, Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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