Molecular characteristics

All heterozygous de novo variants were missense variants absent from gnomAD or other public genomic databases. They were all located in the HLH domain of the protein, crucial for protein dimerization and highly intolerant to missense variations.
Seven individuals had the same homozygous frameshift variant, NP_689627.1: c.221_260del: p.(Gly74AlafsTer18).