PMC8692052_01
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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However, magnetic resonance imaging revealed thoracic spinal cord atrophy (Figure 1).
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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We then investigated the presence of mutations in the SPAST and NEFH genes in the patient's paternal relatives via Sanger sequencing (Figure 2).
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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SPAST mutation is a de novo mutation (PM6, Figure 3).
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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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.