PMC7176811_01
Anterio-posterial Chest and abdominal X-ray on DOL 23. The anterio-posterial chest and abdominal X-ray on DOL23 showed a slightly decreased lung volume with normal lung parenchyma and heart image. The right diaphragm was at the right 6-7 intercostal space and was 1 intercostal space higher than the left side.
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F1
Her chest X-ray image showed normal lung parenchyma but a slightly decreased lung volume (with the right diaphragm at the 6th-7th intercostal space, and the left diaphragm at the 7th-8th intercostal space) (Figure 1).
PMC7176811_02
MUSK mutation analysis and models of the predicted protein structure of MuSK. (A,B) show the MUSK mutations in the patient and her parents, as confirmed by Sanger sequencing. The patient harbored compound heterozygous mutations c.2062C>T (p.Q688X) and c.2324T>C (p.F775S) of the MUSK at exon 14. (A) In the patient, one allele bears the non-sense mutation c.2062C>T (p.Q688X), which was inherited from her father. (B) The other allele bears the c.2324T>C (p.F775S) missense mutation, which was inherited from her mother. (C-E) are the re-constructed three-dimensional (3D) structure of normal MuSK and the predicted MuSK protein structures caused by the 2 mutations. (C) Total view of the 3D structure of normal MuSK. The green dotted line indicates hydrogen bonds between groups. The Phe-775 forms a hydrogen bond with the backbone atoms of Pro-771. (D) The mutation c.2062C>T (p.Q688X) results in a truncation of the protein and disruption of the protein kinase domain structure. (E) The 3D model of the MuSK amino acid substitution of p.F775S (c.2324T>C), from phenylalanine to serine, highlighted by the yellow arrow. The two hydrogen bonds interacting with Pro-771 are formed when Phe-775 is mutated to Ser, which is different from the wild type.
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F2
The result of gene mutation analysis of the infant and her parents by targeted whole-exome next-generation sequencing showed that the infant harbored two novel heterozygous mutations in the MUSK, and were subsequently confirmed by Sanger sequencing (Figures 2A,B). We found that the structures of the protein resulting from these two mutations were predicted and compared with that of the wild type, whereupon significant structural differences were observed (Figures 2C-E).