case_images: PMC10694220_01
case_images: Symptoms, MRL image, and electron photomicrographs of skin biopsy. (A) Thinning hair and eyebrows hair. (B) Loss of axillary hair. (C) Loss of pubic hair and heavy edema of scrotum and both lower limbs. (D) Normal lymphatic trunks, but stagnant contrast media at ankle denoting disruption of lymphatic capillaries ( ). (E) Disruption of tight junctions between endothelial cells of capillaries (blue arrow). (F,G) Fractured capillary walls (red arrows), perivascular neutrophils ( ) and erythrocytes ( ).
case_images: fgene-14-1282711-g001.jpg
case_images: PMC10694220_01_fgene-14-1282711-g001.jpg
case_images: F1
case_images: A 58-year-old man was referred to our hospital in February 2022 with an 8-year history of systemic edema and loss of eyebrow, axillary and pubic hair (Figures 1A-C). Moderate amount of pericardial effusion and large amounts of bilateral pleural and abdominal fluid were found (Supplementary Figure S1). Electron microscopy displayed breakdown of capillary walls (Figures 1E-G). Moreover, magnetic resonance lymphangiography (MRL) of the lower limbs indicated destruction of lymphatic capillaries, although the lymphatic trunk appeared normal (Figure 1D).
case_images: Validation of the missense variant of MYOF in the patient. (A) Sanger sequencing results from the patient and his son. The heterozygous variant in the MYOF gene was identified in the patient (variant), but not in his son (normal). (B) The location of the variant in the protein structure of MYOF. The arrow indicated the mutated site. (C) Amino acid alignment of the MYOF protein from several organisms. The position of Lys1865 residue (highlighted by a red box) was highly conserved among different species. (D) The 3D structure of MYOF protein, and schematic structures of amino acids showed a different steric hindrance of the residue between the WT and the variant.
case_images: fgene-14-1282711-g002.jpg
case_images: PMC10694220_01_fgene-14-1282711-g002.jpg
case_images: F2
case_images: Additionally, histopathological examination of the skin on the right lower limb exhibited perivascular lymphocytic and plasma cell infiltration, along with suspicious mucinous deposits in the dermis (Supplementary Figure S2). Meanwhile, he and his son underwent whole-exome sequencing and Sanger sequencing, respectively, and the patient's genomic DNA sample contained the potentially causal heterozygous mutation (c.5594A>G (p.K1865R)) in the MYOF gene, while his son's did not (Figure 2A). The missense variation resulted in arginine replacing lysine in amino acid sequence 1865, which was in the conserved C2F domain of MYOF in humans and other species. (Figures 2B,C). The 3D structure of MYOF protein was created using the AlphaFold2. The mutant protein showed a different steric hindrance of the residue (the new residue has a smaller size), which may lead to protein misfolding, resulting in pathogenicity (Figure 2D).
case_images: Clinical course of the patient.
case_images: fgene-14-1282711-g003.jpg
case_images: PMC10694220_01_fgene-14-1282711-g003.jpg
case_images: F3
case_images: The clinical course of the patient is shown in Figure 3.