Fig. 1

Sanger sequencing of POLR3B genomic coding sequence and segregation analysis in families. a Patient 1 was heterozygous for a maternally-inherited pathogenic variant, c.1568 T > A (p.Val523Glu), located in exon 15 of POLR3B gene. Father was negative for the variant. The Val523Glu variant has not been reported in the general population databases. While not validated for clinical use, multiple in silico analyses predict that this variant is disease-causing. b Patient 2 was found apparently homozygous for a paternally-inherited pathogenic variant, c.3008G > A (p.Tyr1003Cys), located in exon 26 of POLR3B gene. Father was a heterozygous carrier but mother was negative for the variant, suggesting a deletion on the other allele. The Tyr1003Cys variant has not been reported in the general population databases. While not validated for clinical use, multiple in silico analyses predict that this variant is disease-causing