ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurogenetics
Renpenning Syndrome Caused by c.459_462delAGAG Mutation of polyglutamine-bingding protein 1 and review of the literature
Provisionally accepted
- Department of Pediatrics, Fuyang People's Hospital, Fuyang, China
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Background Renpenning syndrome (OMIM: 309500) is a rare X-linked intellectual disability caused by variations in the polyglutamine-binding protein 1 (PQBP1) gene, characterized by moderate to severe intellectual disability, microcephaly, short stature, lean body, small testes, and abnormal facial features. Methods Comprehensive clinical evaluation and whole exome sequencing were performed to identify the genetic basis of the clinical presentation in a 4-year-7-month-old male proband from a Chinese family. Detected variants underwent validation and familial segregation analysis by Sanger sequencing. Additionally, a literature review was conducted to analyze PQBP1-related genotype-phenotype correlations. Results The proband exhibited typical manifestations of Renpenning syndrome, including severe global developmental delay, microcephaly, short stature, and characteristic facial features. Additionally, he presented with rare anal atresia and co-occurring autism spectrum disorder (ASD). Whole exome sequencing identified a hemizygous PQBP1 variant (c.459_462delAGAG; p.R153Sfs*41) in the proband. Sanger sequencing confirmed this variant was maternally inherited. Conclusion This report describes the first Chinese case of Renpenning syndrome caused by the PQBP1 c.459_462delAGAG variant, presenting with the core phenotype plus anal atresia and ASD. This case expands recognition of the clinical spectrum associated with PQBP1 variants.
Keywords: Renpenning syndrome, Pqbp1, X-linked intellectual disability, Whole exomesequencing, Intellectual Disability
Received: 27 Nov 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Zhang, Mao, Liu, Wang and Ma. 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: Guoshun Mao
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