Spastic paraplegia 51: phenotypic spectrum related to novel homozygous AP4E1 mutation

AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a genetically diverse group of neurologic disorders defined by complex spastic paraplegia. Different forms of AP-4-associated HSP are classified by chromosomal locus or causative gene. Spastic paraplegia 51 (SPG51) is a neurodevelopmental condition that is caused by autosomal recessive mutations in the adaptor protein complex 4 complex subunit 1 (AP4E1) gene. Further, previous studies described an autosomal dominant mutation in the AP4E1 gene has also been linked to persistent stuttering. Here, we describe a patient from a consanguineous marriage who manifested severe intellectual disability (ID), absent speech, microcephaly, seizure, and movement disorders. Exome sequencing identified a novel homozygous frame-shift variant (NM_007347.5:c.3214_3215del, p.Leu1072AlafsTer10) in the AP4E1 gene, which was confirmed by Sanger sequencing. In this study, we also reviewed the phenotype of the former cases. Our findings added to the knowledge of little-studied homozygous AP4E1 mutation.