A Novel 5-bp c.433-1_436delGAGTA (p.Ser145Lysfs*9) Frameshift Deletion in C22orf31 Associated with Global Developmental Delay and Microcephaly in a Saudi Consanguineous Family

Abstract

Intellectual disability (ID) affects approximately 1-3% of the global population, with a higher prevalence reported in consanguineous populations due to autosomal recessive variants. The C22orf31 gene is one of the important candidate genes that is expressed in the brain and is associated with global developmental delays and ID. We aimed to identify the genetic basis of ID, seizure, and microcephaly in a Saudi consanguineous family. Whole exome sequencing was performed on the affected individual from a consanguineous Saudi family, followed by Sanger validation and bioinformatics prediction. Our results showed a novel homozygous 5-base pair (bp) deletion NM_015370.1 (c.433-1_436delGAGTA; p.Ser145Lysfs*9) in the C22orf31 gene. The gene is important and the identified mutation in the C22orf31 gene may disrupt the canonical splice acceptor site and cause a frameshift, leading to a premature termination codon (PTC) that is predicted to trigger nonsense-mediated decay and complete protein loss. The patient manifested developmental delays and seizures along with microcephaly. In conclusion, we report a novel 5-bp deletion in the C22orf31 gene in a Saudi patient. Functional studies and identification of additional families are needed to confirm the role of C22orf31 in disease pathogenesis. This novel finding expands the mutational and clinical spectrum of C22orf31 mutation-related neurodevelopmental disorders in Saudi Arabia.