Pathogenic variants in ZNF668identified to date are biallelic truncating loss-of-function variants
Types of variants reported
All reported variants are nonsense (stop-gain) mutations predicted to result in loss of functional protein:
NM_024706.4:c.1111C > T:p.(Arg371*)
NM_024706.4:c.955C > T;p.(Gln319*)
Suspected pathophysiologic mechanism
ZNF668encodes a zinc-finger protein that plays a key role in the DNA damage response, particularly in homologous recombination repair and chromatin relaxation following DNA damage. Functional studies using fibroblasts from affected individuals show impaired DNA repair, reduced RAD51 foci formation, and decreased cell survival after ionising radiation. Together, these findings support a defect in homologous recombination as the underlying pathophysiologic mechanism.
Diagnostic testing involves:
Option 1: Targeted Gene Testing or Multigene Panel
Sequence analysis of ZNF668(e.g., Sanger sequencing or NGS-based single-gene testing).
Multigene panel testing, such as panels for neurodevelopmental disorders or DNA repair disorders, which include ZNF668among other relevant genes.
Option 2: Comprehensive Genomic Testing
Exome sequencing
Genome sequencing
Inheritance
Autosomal recessive
ZNF668