Heterozygous RNF13 Truncating Variants Are Associated With Developmental and Epileptic Encephalopathy.
Donald R Latner, Susan M Hiatt, Candice R Finnila et al.
✦ AI-curated · Sources linked
Case in brief
The report describes 13 additional individuals with developmental and epileptic encephalopathy 73 associated with RNF13 variants: two had missense variants and 11 had truncating variants. Their findings support and broaden the previously described clinical phenotype, which includes microcephaly, seizures, intellectual disability, developmental delay, limited or absent speech, restricted movement, cortical blindness, and skeletal abnormalities. The authors also identify a narrow region of RNF13 in which truncating variation is poorly tolerated, despite the gene not being highly constrained overall.
What made this case unusual
The findings link RNF13 truncating variants to the disorder and delineate a narrow region intolerant to truncation, even though RNF13 is not highly constrained overall.
Diagnostic / clinical pearl
When evaluating developmental and epileptic encephalopathy, consider RNF13 variants, including truncating variants; their significance may depend on where they occur in the protein.