Approx. 25 single nucleotide variants in the ZNF148 gene have been reported to date (see picture below). Pathogenic mutations concern heterozygous nonsense or frameshift variants, which are almost all located in the last exon (exon 9) of the gene, which correspond to different positions in the ZNF148 protein. The mutations occurred either de novo or were inherited from an affected parent. No genotype-phenotype correlations are currently known but available information suggest complete penetrance with variable expressivity for the mutations described to date.
The pathogenetic mechanism for the nonsense and frameshift variants is not known. These could either lead to haploinsufficiency or yield a truncated protein with altered function, although the former mechanism is more likely.
