Figure 2.

DNA and RNA representations of the intronic SDHC variant c.20 + 74A > G in II.2 of family 1. A, Whole-exome sequencing result of germline DNA as depicted in Integrative Genomics Viewer. The heterozygous substitution of guanine (brown) for adenosine (green) is shown at genomic DNA position 161 284 289. B, RNA sequencing (RNA-Seq) result as depicted in Integrative Genomics Viewer showing alternative splicing of exon 1. The canonical splice site is indicated by the solid red line and the novel splice site by the dotted red line, coinciding with the A > G substitution. C, Junction counts of individual messenger RNA reads showing preferential expression of the aberrantly spliced transcript (n = 114) vs normal transcript (n = 46). D, Electrophoretogram confirming the germline DNA variant. E, Nucleotide, amino acid, and final protein product sequences produced by the 75-bp inclusion observed on RNA-Seq. The start codon is indicated in blue. The intronic inclusion in exon 1 created by the SDHC c.20 + 74A > G variant is indicated in red, and premature stop codons are indicated by the red asterisks.