case_images: PMC9911658_01
case_images: The muscle MRI of lower limbs and abdomen ultrasound. The T1-weight images (A, B) showed slightly atrophy of bilateral lower limbs. Fat suppression (T2-weighted short tau inversion recovery, T2-STIR) images (C, D) have high signal intensity in the bilateral limb muscles, which indicates muscle injury. The abdomen ultrasound (E) showed obvious signs of a fatty liver compared with the health control (F).
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case_images: F1
case_images: Muscle MRI T2 of lower limbs revealed high signal intensity areas in the bilateral lower limb muscles, indicating diffuse muscle injury (Figures 1A-D). Abdomen ultrasound images showed obvious signs of fatty liver (Figure 1E).
case_images: The histopathologic manifestation of the patient's muscle. The formation of vacuoles was found in the muscle fibers for hematoxylin-eosin staining (A). The oil red O staining showed diffuse fat granule aggregation (B).
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case_images: F2
case_images: The results suggested vacuole myopathy with the formation of vacuoles in muscle fibers (Figures 2A, B).
case_images: Sanger traces for PCR products of the proband and his parents. Sanger traces for PCR products of the proband indicated a compound heterozygous mutation in ETFDH gene: c.1034A > G (p.H345R) on exon 9 (A) and c.1448C>A (p.P483Q) on exon 11 (B). Sanger traces for PCR of his parents. The c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11 come from the father and mother (C-F), respectively.
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case_images: F3
case_images: Sanger sequencing showed that these two mutations, respectively, come from the proband's father and mother (Figure 3).
case_images: The bioinformatic analysis of the two mutations observed in the proband. Allelic spectrum and location by the functional domain of reported pathogenic mutations of the ETFDH gene were shown. Multiplex sequence alignment of the ETFDH protein across eight different species shows that H345 and P483 are highly conserved among species (A, C). The structure (B, D) was built by means of homology modeling based on 2 gmh with Identity 95. The structure is modeled by RosettaCM. The partial 3D structures of both mutations revealed polar interaction changes in the ETFDH protein.
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case_images: F4
case_images: Multiplex sequence alignment of the ETFDH protein across eight different species and 100 vertebrate genomes showed that Histidine (H) at codon 345 was highly conserved among species (Figure 4A). The structural analysis showed a polar interaction change between the wild-type and mutant structures of the ETFDH protein (Figure 4B). Multiplex sequence alignment also showed that Proline (P) at codon 483 was highly conserved among species (Figure 4C). The structural analysis revealed a polar interaction change (Figure 4D) and a stability decrease between the wild-type and mutant structures of the ETFDH protein.