PMC5784745_01
Extended family tree illustrating the transmission of Gitelman syndrome over five generations. Males and females are indicated by squares and circles, respectively. Affected subjects are represented by dark symbols. The index patient is V.3.
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A 27-year-old woman (Patient V.3, Figure 1) was admitted to the emergency room after a traffic accident, and the ionogram, assessed for the first time, revealed severe hypokalemia and slight hypomagnesemia (Table 1).
Sequencing chromatograms of the two detected mutations in the SLC12A3 gene are shown and confirmed by classical sequencing Sanger method. (A) NM_000339.2 (SLC12A3): c.1805_1806delAT (p.Tyr602Cysfs*31); EX14; Hom et (B) NM_000339.2 (SLC12A3): c.2660+1G>A; IVS22; Hom zygosity: Hom represents a homozygous mutation, Het represents a heterozygous mutation.
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Analysis of the family tree revealed that the father's grandmother and the mother's grandfather were siblings (Figure 2). The two detected mutations by NGS were confirmed by the Sanger method (Figure 2). The first mutation (Figure 2A), homozygous, is a frameshift c.1805_1806delAT (with reference sequence NM_000339.2), producing a deletion of two nitrogenous bases: The second mutation (Figure 2B), c.2660+1G>A causes substitution of guanine and adenine at a 5' splice site of intron 22 (IVS22+1G>A) deletion of exon 22, and frameshift at exon 23, causing aberrantly spliced transcripts.