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.

KMT5B基因编码一种参与染色质重塑的赖氨酸甲基转移酶，该基因的致病变异已被证实与智力障碍、孤独症谱系障碍及多种畸形特征相关。然而，其具体的基因型-表型关联尚未完全阐明。本研究报道1例4岁男性患者，该患者表现为发育迟缓、社交互动障碍、重复行为及语言发育延迟。全外显子组测序检出KMT5B基因上1个新的杂合移码变异（c.618del; p.Glu206Aspfs*7）。家系分离分析显示，患者父亲同样携带该变异，且存在智力障碍与强迫障碍。本研究拓展了与KMT5B单倍体不足相关的突变与表型谱，同时也提示KMT5B相关疾病的神经精神表型可能持续至成年阶段，强调了对受累个体开展长期随访与更全面的神经行为评估的必要性。