PMC5388735_01
Neuroimaging and cytological features identified in ChAc patients.
(A) Axial and coronal view of the basal ganglion plane in patient 1 (left) and patient 2 (right) demonstrated similar MR imaging features: caudate nucleus head atrophy and anterior horn dilation of lateral ventricles (marked by arrows). (B) Acanthocytes (marked by arrows, Giemsa staining) were detected in peripheral blood smear under light microscope examination. The average acanthocytes ratio in patient 1 and 2 were 18% (left) and 17% (right), respectively. (C) Schematic diagram of striatal atrophy pattern in ChAc patient. The caudate nucleus head atrophy demonstrated a dorsal to ventral pattern (marked by yellow), while the putamen presented a caudate to rostral mode (marked by black).
fnagi-09-00095-g001.jpg
PMC5388735_02_fnagi-09-00095-g001.jpg
F1
Subsequently, three repeated and independent peripheral blood smears conformably detected acanthocytes, with acanthocytes ratio averaged to 17% of CBC (see Figure 1B-right column). MRI scanning demonstrated mild atrophy in the caudate head and putamen bilaterally, accompanying moderate anterior horn dilation of lateral ventricles (see Figure 1A-right column). Moreover, the VPS13A gene sequencing further confirmed the diagnosis, revealing a heterozygous nonsense mutation (c.8282C>G p.Ser2761Ter) in exon 60 and a heterozygous splicing mutation (c.9276-1G>A) in intron 69 (see Figure 2B and Table 1).
Sequencing analysis of the VPS13A gene in ChAc patients and family member.
(A) High-throughput sequencing of VPS13A gene (NM_033305) in patient 1 reveals a 5 bp heterozygous deletion (c.7276_7280delCAATA) in exon 52 (A1) and a substitution of T for C (c.8278C>T) in exon 60 (A2). Moreover, the frameshift mutation and nonsense mutation have been confirmed by the Sanger sequencing method precisely. (B) Chip capture high throughput sequencing of VPS13A gene (NM_033305) in patient 2 shows a substitution of G for C (c.8282C>G) in exon 60 (B1) and an aberrant splicing pattern (c.9276-1G>A) in intron 69 (B2). While, in contrast, her daughter only shows a heterozygous splicing mutation similar to her mother's in intron 69 (c.9276-1G>A) (B2), but not the nonsense one in exon 60 (B1).
fnagi-09-00095-g002.jpg
PMC5388735_02_fnagi-09-00095-g002.jpg
F2
MRI scanning demonstrated mild atrophy in the caudate head and putamen bilaterally, accompanying moderate anterior horn dilation of lateral ventricles (see Figure 1A-right column). Moreover, the VPS13A gene sequencing further confirmed the diagnosis, revealing a heterozygous nonsense mutation (c.8282C>G p.Ser2761Ter) in exon 60 and a heterozygous splicing mutation (c.9276-1G>A) in intron 69 (see Figure 2B and Table 1). Nevertheless, the VPS13A gene sequencing in this patient's daughter, a healthy girl with no sign of ChAc, identified a heterozygous splicing mutation similar her mother's in intron 69 (c.9276-1G>A) (see Figure 2B).
PMC5388735_02
Neuroimaging and cytological features identified in ChAc patients.
(A) Axial and coronal view of the basal ganglion plane in patient 1 (left) and patient 2 (right) demonstrated similar MR imaging features: caudate nucleus head atrophy and anterior horn dilation of lateral ventricles (marked by arrows). (B) Acanthocytes (marked by arrows, Giemsa staining) were detected in peripheral blood smear under light microscope examination. The average acanthocytes ratio in patient 1 and 2 were 18% (left) and 17% (right), respectively. (C) Schematic diagram of striatal atrophy pattern in ChAc patient. The caudate nucleus head atrophy demonstrated a dorsal to ventral pattern (marked by yellow), while the putamen presented a caudate to rostral mode (marked by black).
fnagi-09-00095-g001.jpg
PMC5388735_02_fnagi-09-00095-g001.jpg
F1
Subsequently, three repeated and independent peripheral blood smears conformably detected acanthocytes, with acanthocytes ratio averaged to 17% of CBC (see Figure 1B-right column). MRI scanning demonstrated mild atrophy in the caudate head and putamen bilaterally, accompanying moderate anterior horn dilation of lateral ventricles (see Figure 1A-right column). Moreover, the VPS13A gene sequencing further confirmed the diagnosis, revealing a heterozygous nonsense mutation (c.8282C>G p.Ser2761Ter) in exon 60 and a heterozygous splicing mutation (c.9276-1G>A) in intron 69 (see Figure 2B and Table 1).
Sequencing analysis of the VPS13A gene in ChAc patients and family member.
(A) High-throughput sequencing of VPS13A gene (NM_033305) in patient 1 reveals a 5 bp heterozygous deletion (c.7276_7280delCAATA) in exon 52 (A1) and a substitution of T for C (c.8278C>T) in exon 60 (A2). Moreover, the frameshift mutation and nonsense mutation have been confirmed by the Sanger sequencing method precisely. (B) Chip capture high throughput sequencing of VPS13A gene (NM_033305) in patient 2 shows a substitution of G for C (c.8282C>G) in exon 60 (B1) and an aberrant splicing pattern (c.9276-1G>A) in intron 69 (B2). While, in contrast, her daughter only shows a heterozygous splicing mutation similar to her mother's in intron 69 (c.9276-1G>A) (B2), but not the nonsense one in exon 60 (B1).
fnagi-09-00095-g002.jpg
PMC5388735_02_fnagi-09-00095-g002.jpg
F2
MRI scanning demonstrated mild atrophy in the caudate head and putamen bilaterally, accompanying moderate anterior horn dilation of lateral ventricles (see Figure 1A-right column). Moreover, the VPS13A gene sequencing further confirmed the diagnosis, revealing a heterozygous nonsense mutation (c.8282C>G p.Ser2761Ter) in exon 60 and a heterozygous splicing mutation (c.9276-1G>A) in intron 69 (see Figure 2B and Table 1). Nevertheless, the VPS13A gene sequencing in this patient's daughter, a healthy girl with no sign of ChAc, identified a heterozygous splicing mutation similar her mother's in intron 69 (c.9276-1G>A) (see Figure 2B).