(A) Pedigree with 5 generations (I–V) of a Brazilian family with autosomal dominant hypomagnesemia. Affected family members are indicated in black; males and females are indicated by squares and circles, respectively. A diagonal line indicates that the individual is deceased. Numbers in red indicate individuals included in the Sequence Tagged Site (STS) mapping. (B) 10K SNP array–based haplotyping analysis was performed that showed linkage to a 14.3-cM region between SNP rs717596 and rs252028 on the short arm of chromosome 12. This region was confirmed and narrowed down with STS markers to a 11.6-cM region between markers D12S1626 and D12S1623 containing 31 genes, including KCNA1. (C) KCNA1 encodes the voltage-gated potassium channel Kv1.1. Mutation analysis of KCNA1 revealed a heterozygous A763G missense mutation in affected individual III-1 that results in a N255D amino acid substitution (underlined). (D) Multiple alignment analysis shows conservation of the N255 amino acid (red bar) among species and Kv1 family members. Mutated amino acids in other families with the Kv1.1 genotype are indicated by dark blue dots (17, 19, 21, 22). Blue and black letters represent conserved and nonconserved amino acids, respectively. (E) Schematic representation of the Kv1.1 channel, which consists of a voltage sensor in transmembrane segment S4 and a pore-forming region (S5 and S6). Localization of the newly identified N255D mutation is denoted by the red dot, while other nearby mutations are indicated by dark blue dots.