Expansion of the Phenotypic Spectrum of TNRC6B-Related Neurodevelopmental Disorder in a Three-Generation Family with 22q11 Region

TNRC6B (heterozygous pathogenic variant, 22q11 locus)

Heterozygous loss of function of TNRC6B, central effector of the RNA-induced silencing complex (RISC); TNRC6B is essential for miRNA-mediated post-transcriptional regulation; pathogenic variants cause NDD with variable penetrance

Description of a three-generation family carrying a heterozygous pathogenic variant in TNRC6B, a central effector of the RISC complex involved in miRNA regulation. The phenotypic spectrum includes mild-to-moderate intellectual disability, language disorders, dyspraxia, and remarkable expressivity variability between family members. This article expands the known spectrum of TNRC6B NDDs and demonstrates autosomal dominant penetrance with variable expressivity.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

TNRC6B is a recently associated AD NDD gene whose spectrum is progressively expanding. Familial phenotypic variability underscores the importance of nuanced genetic counseling. Include in NDD panels and analyze in family context.

phenotypic expansion 3 generations +2; documented miRNA mechanism +2; clinical expressivity variability +2; Genes +1