Figure 3.

Pedigree Structures and Clinical Features of Additional Families With SCN5A Mutations

Haplotypes at the chromosome 3p locus where SCN5A is located are shown. Each shaded haplotype defines a chromosomal segment that harbors a mutant SCN5A gene. In 2 families, point mutations caused amino acid substitutions: D1595H in DC-30 and T220I in DC-31. In DC-26, the insertion of 2 bases in the mutant gene results in a truncated protein that terminates in a string of 18 anomalous amino acids (fs851 [frameshift at amino acid 851]; Figure 2C). In DC-96, neither of the proband’s parents and none of her 7 siblings had cardiac disease. The haplotypes she inherited from her father (dark blue) and mother (light purple) are also inherited by other siblings, yet she is the only family member with a mutation in SCN5A. These findings indicate that the point mutation, R814W, arose as a spontaneous, or de novo, event on either the paternal or maternal chromosome. SVT indicates supraventricular tachycardia.