A Previously Unreported POU3F3 p.(Lys409Ter) Variant in Snijders Blok–Fisher Syndrome: Mechanistic Context of Expressed Truncating Alleles

Background: Snijders Blok–Fisher syndrome (SNIBFIS; OMIM #618604) is a rare neurodevelopmental disorder associated with heterozygous POU3F3 variants and characterized by developmental delay, prominent speech and language impairment, behavioral abnormalities, and dysmorphic features. Case Presentation: We report a Chinese boy evaluated at 7 years and 9 months for longstanding developmental and language delay. He walked independently at 18 months, began using meaningful single words at approximately 24 months, and remained unable to produce complete sentences at 7 years of age. Wechsler intelligence testing yielded a full-scale IQ of 57. Clinical evaluation documented attention-deficit/hyperactivity disorder and autism spectrum disorder, with a Childhood Autism Rating Scale score of 38. Additional findings included sleep-onset difficulty, low-set ears, an open-mouth appearance, a single transverse palmar crease, and left hyperopia. He had no history of seizures, and electroencephalography was normal. Trio whole-exome sequencing identified a heterozygous POU3F3 nonsense variant, NM_006236.3:c.1225A>T [p.(Lys409Ter)], absent from both parental blood samples and reported as de novo by the diagnostic laboratory. The variant was not identified in the published literature or publicly accessible variant resources searched through 8 September 2026. Conclusions: This case adds to the reported POU3F3 variant spectrum and illustrates the importance of considering the unusual behavior of truncating alleles in this intronless gene.