case_images: PMC8692052_01
case_images: Magnetic resonance imaging (MRI) of the thoracic spinal cord. The gray arrow indicates the site of the thoracic spinal cord was smaller than the healthy people.
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case_images: fig1
case_images: However, magnetic resonance imaging revealed thoracic spinal cord atrophy (Figure 1).
case_images: Sanger sequencing results of the SPAST and NEFH genes of the patient's family. (a) Mutation in the SPAST gene in a Chinese family. (b) Mutation in the NEFH gene in a Chinese family.
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case_images: PMC8692052_01_CRIG2021-6636855.002.jpg
case_images: fig2
case_images: We then investigated the presence of mutations in the SPAST and NEFH genes in the patient's paternal relatives via Sanger sequencing (Figure 2).
case_images: Pedigree of the patient's family. The gray arrow indicates the proband II:5 of the SPAST and NEFH mutations. Squares indicate males, and circles indicate females. Individuals carrying the NEFH mutation are represented by black-filled symbols, whereas empty symbols indicate healthy individuals without the NEFH or SPAST mutation. The presence of the SPAST mutation alone was not observed in any family member.
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case_images: fig3
case_images: SPAST mutation is a de novo mutation (PM6, Figure 3).
case_images: Sequence conservation analysis of the SPAST gene. Spastin protein sequence alignment across species showing the area of the amino acid substitution (red frame) and the surrounding residues.
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case_images: fig4
case_images: This mutation was located in a conservative site (Figure 4) and was present in the functional domain of the AAA + ATPase domain, which is essential for the function and activity of enzymes and is a hotspot of pathogenic variants (PM1). Taken together, we identified the ACMG criteria for this mutation as PS1, PM1, PM2, PM6, and PP3, indicating that this variant is pathogenic.