Variant in the AP1G1 gene associated with phenotypic features of Usmani-Riazuddin syndrome: first Brazilian case report

Abstract

Pathogenic variants in the AP1G1 gene (MIM* 603533) have recently been linked to Usmani-Riazuddin syndrome (USRISR, MIM# 619548; USRISD, MIM# 619467), a very rare genetic condition characterized by multisystem involvement. This syndrome manifests with symptoms such as intellectual disability, speech and developmental delays, and behavioral anomalies. The AP1G1 gene plays a crucial role in producing the 822-amino-acid subunit of gamma-adaptin (γ) within the AP-1 complex (AP1γ). In this report, we present a Brazilian boy who exhibits moderate intellectual impairment, overall developmental delay, autistic features, aggressive behavior, and an absence of speech with a previously reported variant in the AP1G1 gene (c.44G>A; p.Arg15Gln). This case marks the first Brazilian case and the fourth documented instance of Usmani-Riazuddin syndrome associated with an AP1G1 variant. Our findings contribute to the understanding of the phenotypic characteristics of this condition and further assert the association between the AP1G1 gene and Usmani-Riazuddin syndrome.