Figure 2.

Validation of the SEC24D Mutations by Sanger Sequencing of Genomic DNA

Pedigrees of the two analyzed families and electropherograms of the respective SEC24D mutations in exons 5, 22, and 23 are shown. In family 1, each parent carries one of the two mutations and the affected son (I-4) is compound heterozygous for the SEC24D mutations c.613C>T (p.Gln205^∗) and c.3044C>T (p.Ser1015Phe). The healthy sister of the affected individual did not carry either of the two mutations. Also in family 2, each parent is heterozygous carrier of one of the two SEC24D mutations and both affected fetuses (II-3 and II-4) are compound heterozygous for c.2933A>C (p.Gln978Pro) and c.3044C>T (p.Ser1015Phe). The healthy sister (II-5) is a heterozygous carrier of only one of these mutations. The red arrows in the electropherograms indicate either the mutation or the respective position in the wild-type sequence. In addition, for several family members the haplotype combination at the SEC24D locus is shown, and 15 of the 166 consecutive good-quality SNPs used for reconstructing the 14 Mb disease haplotype are depicted. Note that individuals I-2, I-4, and II-1 share the SEC24D mutation c.3044C>T and an identical haplotype between the SNPs rs6533681 and rs2255457. The dashed line between I-2 and II-2 indicates that the mutation c.3044C>T is a founder mutation inherited from a distant common ancestor.