Autosomal recessive spinocerebellar ataxia type 4 with a VPS13D mutation: A case report

Figure 1 Pedigree of the patient’s family. The patient’s parents and sister were all healthy. Males and females are represented as squares and circles, respectively. The patient is indicated by black-filled symbols, and unfilled symbols indicate the unaffected individuals. The mutation state is given below.

Figure 2 Brain magnetic resonance imaging. The image on the left is the T1-weighted axial image, the image in the middle is the T2-weighted axial image, and the image on the right is the T2-weighted sagittal image. No cerebellar atrophy was observed.

Figure 3 Genomic sequence electropherograms. The patient carried a novel c.3288delA (p.Asp1097ThrfsTer6) frameshift mutation of the VPS13D gene, which was not detected in Chinese databases. Only the patient’s father was heterozygous for this mutation among her parents and sister, and her mother was heterozygous for c.12485C>A (p.Thr4162Asn). Pedigree analysis suggested that the disease was consistent with autosomal recessive inheritance.

Figure 4 Conservation of amino acids in the context of the frameshift mutation. Amino acid sequence alignments of some of the amino acids affected by the mutation are shown for selected species. The red rectangle highlights the first amino acid affected by the frameshift mutation. This novel mutation is located in a relatively conserved domain.

Figure 5 Schematic representation of the VPS13D protein (RefSeq NM_015378). The novel p.Asp1097ThrfsTer6 mutation is marked red. The others are mutations that have since been found in other studies: p.Ser405Arg, p.Thr1118Met, p.Arg3141*, and p.Thr2945Ala (Koh et al[13], 2020); p.Gly1190Asp, p.Ala4210Val, p.Met1307Leu, p.Gly4149Ser, p.Asn4107Ile, p.Gln1106Ter, p.Tyr1803Ter, p.Gln662Ter, p.Gln2572Ter, p.Val2987Glyfs*14, and p.Leu2277Ter (Seong et al[7], 2018); p.Val2445Glufs*16, p.Leu2900Ser, p.Asn3521Ser, p.Glu3573Aspfs*3, p.Arg4228Gln, p.Arg3253Gln, p.Leu2900Ser, p.Thr865Ala, p.Arg674Gly, and p.Gly1200Asp (Gauthier et al[12], 2018); p.Arg260Trp (McCarthy et al[14], 2014); p.Arg674Gly (Shamseldin HE et al[16], 2017); and p.Leu2587Pro (Lee JS et al[15], 2020). N1: VPS13 1st N-terminal domain (aa 2-115); N2: VPS13 2nd N-terminal domain (aa 137-356); U: Ubiquitin-associated (UBA)-like domain (aa 2627-2679); SHR: VPS13 SHORT ROOT transcription factor-binding domain (aa 3276-3558); C: VPS13 C-terminal domain (aa 3983-4129).