Molecular genetic investigation revealed a missense mutation (p.Ile124Val) in the GPD1L gene.
Amplification of the coding regions of the GPD1L gene (Refseq accession number NM015141.3; primer designs based on ) and subsequent sequencing revealed a heterozygous missense mutation in exon 4: c.370A>G, p.Ile124Val (Figure 1).
After genetic counselling, DNA was obtained from the father, mother and sister and these were tested for the presence of the mutation c.370A>G, p.Ile124Val, in the GPD1L gene.
It demonstrates a possible link between dead-in-bed syndrome and Brugada syndrome, thereby supporting earlier work , albeit for a GPD1L gene variant of unclear clinical significance but with supportive in vitro evidence.
Mutations in the GPD1L gene were first reported in 2007 to be causative of sudden infant death and familial Brugada syndrome [6,7].
In contrast, bioinformatic analysis of the mutation event at the protein level predicts a benign as well as a disease-causing effect, while three programmes predict no effect regarding splicing of the GPD1L gene transcript and one predicts an effect on SR protein binding sites (Table 1).
The latter three genes are involved in gluconeogenesis/glycogenolysis, dysautonomia, and endothelial cell function, respectively; however, they did not analyze the GPD1L gene or any of the other Long QT genes.
Abbreviations CTGF: Gene encoding for connective tissue growth factor G6PC: Gene encoding for glucose-6-phosphatase GPD1L: Gene glycerol-3-phosphate dehydrogenase 1-like protein PHOX2B: Gene encoding for paired mesoderm homeobox protein 2b SCN5A: Gene encoding for sodium channel protein type 5 subunit alpha, isoform a [Na.sub.v] Sodium ion channel protein, voltage-gated, type V, 1.5: alpha subunit.