Renpenning syndrome caused by the c.459_462delAGAG mutation in PQBP1: a case report and literature review.

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 frameshift variant, NM_001032382.2:c.459_462delAGAG (p.Arg153fs) (VCV000010980.79), 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.