Figure 4.

Molecular genetic findings of the ADOA patients. ((a) and (b)) Sequence chromatograms of the wild-type allele and the mutant allele (Patient 1-II-1) are shown. In the mutant allele (b), a heterozygous C to T (reverse strand) mutation, indicated by a vertical arrow, is shown at the −1 position of intron 18 (c.1771-1G>A). ((c) and (d)) Sequence chromatograms of the wild-type and the mutant (Patient 1-II-1) cDNAs from white blood cells are shown. Entire exon 19 is skipped in the mutant mRNA (d). Skipping exon 19 leads to a deletion of 77 bp of mRNA of OPA1 gene and a resulting frameshift in the product (p.N591GfsX18). (e) Schematic diagram of the splicing error in Patient 1-II-1 is shown. As a result of G to A mutation at position −1 of intron 18, whole exon 19 is skipped in the mutant gene. ((f) and (g)) Sequence chromatograms of the wild-type allele and the mutant allele (Patient 2-II-1) are shown. In the mutant allele (g), a heterozygous one base-pair deletion indicated by a vertical arrow can be seen (c.1899delT). ((h) and (i)) Sequence chromatograms of the wild-type allele and the mutant allele (Patient 3-III-1) are shown. In the mutant allele (i), a heterozygous C to T mutation, indicated by a vertical arrow, is shown (c.1096C>T). ((j) and (k)) Sequence chromatograms of the wild-type allele and the mutant allele (Patient 4-II-1) are shown. In the mutant allele (g), a heterozygous one base-pair deletion, indicated by a vertical arrow, is shown (c.1102delA).