TRPM4 missense mutation in exon 1 associated with PFHBI.
(A) Relative expression of TRPM4 transcripts in different tissues of nondiseased human heart was assayed by quantitative RT-PCR. TRPM4 mRNA expression levels were normalized to the level in left ventricle. Numbers of individual probes are shown in parentheses. Each experiment was done in triplicate. (B) Electropherograms show TRPM4 WT sequence and the heterozygous sequence change c.19G→A in the DNA of PFHBI-affected individuals. (C) Partial amino acid sequence alignment of TRPM4 N terminus among different species. Gray shading shows the conserved sequence motif; red shading highlights the glutamic acid substituted by lysine in TRPM4 associated with PFHBI. Numbering refers to the human sequence. (D) Diagram of TRPM4 topology and functional domains, with 6 membrane-spanning domains (TM) flanked by N- and C-terminal cytoplasmic sequences. PFHBI, PFHBI domain; CaM, Calmodulin-binding domain; WB, Walker B ATP-binding motif; CCR, coiled-coiled region. Figure part adapted with permission from Pflügers Archiv (19).