Background: Adaptor protein complex-4 (AP-4), a heterotetrameric protein complex, plays an important role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with spastic tetraplegia, developmental delay and intellectual disability (ID).
Case presentation: We report on a Chinese patient with infantile spasms, infantile hypotonia and global developmental delay. Exome sequencing showed compound heterozygous mutations in AP4M1(c.19A>G, p.I7V and c.137C>T, p.P46L).
Conclusions: This is the first case of biallelic missense variants lay on the region encoding LH domain, which is important for membrane trafficking via protein–protein and intramolecular binding specificities. Our study expands the molecular spectrum associated with AP-4 deficiency syndrome, and reviews the clinical features of reported patients with AP4M1 mutations.