Supplementary Material for: A Novel KMT5B Frameshift Variant Presenting with Autism and Psychiatric Features: Intra-Familial Phenotypic Variation – A Case Report

Pathogenic variants in the KMT5B gene, encoding a lysine methyltransferase involved in chromatin remodeling, have been associated with intellectual disability, autism spectrum disorder, and various dysmorphic features. However, the detailed genotype-phenotype correlations have yet to be fully elucidated. We report a four-year-old male patient who presented with developmental delay, impaired social interaction, repetitive behaviors, and language delay. Whole-exome sequencing identified a novel heterozygous frameshift variant in KMT5B (c.618del; p.Glu206Aspfs*7). Segregation analysis revealed that the patient's father also carried the same variant and exhibited intellectual disability and obsessive-compulsive disorder. This expands the mutational and phenotypic spectrum associated with KMT5B haploinsufficiency. It also underscores the potential for neuropsychiatric manifestations of KMT5B-related disorders to persist into adulthood, emphasizing the need for long-term follow-up and broader neurobehavioral assessment in affected individuals.