Case Study and Literature Review of Phelan-McDermid Syndrome Caused By a Pathogenic Mutation in The SHANK3 Gene

Abstract Background: Phelan-McDermid syndrome is a rare genetic disorder resulting from heterozygous deletion of 22q13.3 with the involvement of at least part of SHANK3 or a heterozygous pathogenic variant in SHANK3. We would like to explore the possible pathogenesis and therapeutic direction of PMS.Methods: We identified a child who harbored a de novo SHANK3 gene mutation and had a speech delay and mental retardation. This pathogenic mutation (c.3679dup, p.A1227Gfs*69) may lead to early termination of protein transcription and is speculated to cause changes in protein function. The gene expression profiles of family members were evaluated by RT-PCR, which showed that SHANK3 expression was significantly lower in the child than in the other family members. The sites of pathogenic and likely pathogenic mutations in the SHANK3 gene reported by ClinVar were searched, and the mutation sites were summarized and marked. Results: The relevant literature was reviewed to understand the current state of research progress and possible future treatment directions. Researchers have found that CDPPB is a potent and selective positive allosteric modulator of mGluR5. In addition, it is important to further study whether NMD is involved in the expression of SHANK3 and to further investigate PTCs.Conclusions: Genetic testing is essential for children with development delay. It’s necessary to do further research about the therapeutic direction.