A novel splice site mutation in AP1S2 gene for X‐linked mental retardation in a Chinese pedigree and literature review

BACKGROUND: Pettigrew syndrome (PGS) is a rare X‐linked mental retardation that caused by AP1S2 mutation. The pathogenesis of AP1S2 deficiency has remained elusive. The purpose of this study is to give a comprehensive overview of the phenotypic and genetic spectrum of AP1S2 mutations. METHODS: This study systematically analyzed clinical features and genetic information of a Chinese family with AP1S2 variation, and reviewed previously reported literatures with the same gene variation. RESULTS: We identified a new c.1‐1 G>C mutation in AP1S2 gene from a four generation family with seven affected individuals and found the elevated neuron‐specific enolase (NSE) in a patient. We summarized the clinical manifestation of 59 patients with AP1S2 mutation. We found that pathogenic point mutations affecting AP1S2 are associated with dysmorphic features and neurodevelopmental problems, which included highly variable mental retardation (MR), delayed in walking, abnormal speech, hypotonia, abnormal brain, abnormal behavior including aggressive behavior, ASD, self‐abusive, and abnormal gait. Patients with splice site mutation were more likely to lead to seizures. By contrast, patients with nonsense mutations are more susceptible to microcephaly. CONCLUSION: Our findings suggest AP1S2 mutations contribute to a broad spectrum of neurodevelopmental disorders and are important in the etiological spectrum of PGS.