PMC9884671_01
The echocardiogram demonstrated the thickening of the myocardium (the red arrows showed the hypertrophic interventricular septum and posterior wall of the left ventricle).
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F1
Echocardiography revealed the features suggesting HCM (Figure 1).
(A) Pedigree of the family reported in the present study. The arrow depicts the proband. The circles correspond to the women. The squares indicate the men. (B) Direct sequencing showing the novel missense variant c.1081T > A of the MIPEP gene. (C) The mtDNA copy numbers in healthy controls (n = 3) and the proband. A notable reduction in the mtDNA level was noted in the proband (NC, normal control, **P < 0.01). (D) Structural visualization of the identified MIPEP missense alteration using Alpha Fold structure of the human MIPEP as a template (Identifier:AF-Q99797-F1). The variant site and the relevant residues were shown as sticks (the variant site is shown in magenta and the relevant residues are shown in aquamarine). The yellow dotted line represents the H-bond that connects the variant site with the residues. (E) Alignment of MIPEP orthologs in different species around the mutated amino acids residues. Hs, Homo sapiens; Pt, Pan troglodytes; Mm, Macaca mulatta; Bt, Bos taurus; Rn, Rattus norvegicus; Gg, Gallus gallus; Sc, Saccharomyces cerevisiae S288C; Sp, Schizosaccharomyces pombe.
(F)
MIPEP gene exons RT-qPCR analysis showed a heterozygous loss of exons 1, 10, and 19 in the proband and his mother.
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F2
Tyr361Asn) and a 1.12-Mb deletion (chr13:23777833-24895906) containing the entire gene (Figures 2A, B), neither of which has been previously reported. And the result showed that the relative ratio of mtDNA copy number of the proband was significantly decreased by 71.5%, compared to that in the healthy controls (p < 0.001; Figure 2C).