Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With...

To date, only one study describes three unrelated cases of neurodevelopmental disorders associated with duplications in 22q13.2, which include the TCF20 gene. In contrast, TCF20 variants and deletions are well characterized. Here, we report six new cases of 22q13.2 gain, including TCF20, identified through array-comparative genomic hybridization (array-CGH). Probands exhibited neurodevelopmental delay, and several presented with facial dysmorphism, abnormal growth parameters, and abnormalities affecting the skeletal, respiratory, genitourinary, and/or cardiovascular systems. We documented one 440 Kb triplication and five cases of duplication ranging from 82.5 Kb to 3.03 Mb in size. Co-segregation analysis of the CNV and clinical symptoms supports variable expressivity. However, the complete penetrance of these gains remains questionable compared to the known pathogenic variants and structural variations associated with loss of function. We discuss the genotype-phenotype correlations and hypotheses surrounding the impairment of TCF20 protein function.