Clinical and Genetic Analysis of a Chinese Patient Carrying a Novel POGZ Variant Associated with White-Sutton Syndrome

<i>Background:</i> White-Sutton Syndrome (WSS) is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the <i>POGZ</i> gene, which is essential for chromatin remodeling and neuronal development. Because of its broad phenotypic heterogeneity and lack of disease-specific features, early diagnosis and <i>management remain challenging.</i> Timely genetic testing can significantly aid in early diagnosis and intervention, improving patient outcomes.<i> Objective:</i> To describe the clinical and genetic findings of a Chinese pediatric patient with a novel <i>POGZ</i> mutation, summarize the diagnostic approach, and underscore the importance of early genetic testing and multidisciplinary management for the diagnosis and management of WSS. <i>Method: </i>A 4-month-old male infant presented with developmental delay and abnormal liver function. Comprehensive clinical, imaging, auditory, and ophthalmologic evaluations were performed. Whole-genome sequencing and Sanger validation were conducted, followed by multidisciplinary management including nutritional therapy and early rehabilitation. <i>Result: </i>The patient exhibited microcephaly, hypotonia, distinctive facial dysmorphism, auditory impairment, and retinitis pigmentosa. Brain MRI revealed hypoplasia of the corpus callosum. A novel heterozygous frameshift mutation c.2699_2700dup (p.Leu901TyrfsTer2) in <i>POGZ</i> was identified and classified as pathogenic according to ACMG criteria (PVS1 + PS2 + PM2 + PP4). The variant was not reported in existing genetic databases, representing a novel pathogenic mutation expanding the <i>POGZ</i> mutational spectrum. Despite multidisciplinary rehabilitation, neurodevelopmental progress remained limited. <i>Conclusion: </i>This report documents the first Chinese case of White-Sutton Syndrome caused by a novel<i> POGZ</i> frameshift mutation, emphasizing the importance of early genetic testing for accurate diagnosis and timely intervention. Genetic diagnosis combined with personalized rehabilitation may improve long-term neurodevelopmental outcomes for patients with WSS. This case study expands the mutation spectrum of the <i>POGZ</i> gene and provides valuable reference for the diagnosis, treatment, prognosis assessment, and genetic counseling of WSS patients.