Dataset Information

Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.

ABSTRACT:

Background

Chorea-acanthocytosis (ChAc) is a rare hereditary autosomal recessive neurodegenerative disorder caused by pathogenic variants of the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The variant spectrum of VPS13A has not been completely elucidated. This study reports two novel heterozygous VPS13A pathogenic variants in ChAc that expand the variant spectrum of VPS13A.

Case presentation

We described a case of a 29-year-old man with typical clinical manifestations of ChAc, including chorea, orofacial lingual dyskinesia, vocal tics, elevated serum biochemical indicators, increased acanthocytes in peripheral blood, and caudate nucleus atrophy. Next-generation sequencing revealed two heterozygous variants of VPS13A: a nonsense variant (NM_033305.2: c.8215G > T, p. Glu2739Ter) and a deletion variant in the exons 25-31.

Conclusion

The identified nonsense variant gives rise to premature translation termination, while the deletion variant is expected to cause a significant in-frame deletion of amino acid residues in the encoded protein. Both variants are considered to be pathogenic and result in loss-of-function proteins. These findings have implications for the genetic counseling of patients with VPS13A variants.

SUBMITTER: Chen X

PROVIDER: S-EPMC10548615 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.

Chen Xi X Zhang Piao P Wang Lijuan L Zhang Yuhu Y

BMC neurology 20231004 1

<h4>Background</h4>Chorea-acanthocytosis (ChAc) is a rare hereditary autosomal recessive neurodegenerative disorder caused by pathogenic variants of the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The variant spectrum of VPS13A has not been completely elucidated. This study reports two novel heterozygous VPS13A pathogenic variants in ChAc that expand the variant spectrum of VPS13A.<h4>Case presentation</h4>We described a case of a 29-year-old man with typical clinical manifestations of ...[more]

PMID: 37794323

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Project description:Background and objectivesThe diseases historically known as neuroacanthocytosis (NA) conditions include VPS13A disease (formerly chorea-acanthocytosis) and XK disease (formerly McLeod syndrome). Here we report a patient with a hyperkinetic syndrome associated with variants in VPS13A with a concomitant homozygous nucleotide expansion in Replication factor C, subunit 1 (RFC1) and evaluate the role of ektacytometry for the assessment of acanthocytes.MethodsInvestigations included clinical assessments, neuroimaging studies, laboratory analyses, blood smears, ektacytometry, psychometric evaluation, and genetic analyses. Using ektacytometry, an osmoscan curve is obtained yielding a diffraction pattern as a measure of average erythrocyte deformability from circular at rest to elliptical at a high shear stress. The pattern allows the derivation of several parameters (mainly EI-max, O-min and O-Hyper points). Samples from two other patients with genetically proven VPS13A disorder and XK disease and varying numbers of acanthocytes as well as from a fourth with acanthocytosis due to liver failure were also analyzed.Case presentationThe patient has impulsivity, chorea and disabling feeding dystonia refractory to treatment and 15% acanthocytes in peripheral blood. Genetic workup revealed compound heterozygous variants c.1732_1733del; p.(V578Ffs*9) and c.8282C > A, p.(S2761*) in VPS13A with absence of chorein in the blood, the latter variant is novel. In addition, he harbors a homozygous nucleotide expansion in the RFC1 gene, reported in cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). However, the patient does not display ataxia yet. Ektacytometry revealed significantly reduced erythrocyte deformability in this patient and in another man with VPS13A disease. In contrast, the patient with XK disease had 2% acanthocytes and mild abnormalities on ektacytometry. In the three cases, ektacytometry yielded a specific pattern, different from acanthocytosis due to liver failure.ConclusionPathogenicity of the VPS13A variants is confirmed by absence of chorein, long-term follow up is required to evaluate any synergistic impact of for the underlying CANVAS mutation. New generation ektacytometry provides an objective measurement of erythrocytes' rheological properties and may serve as a complement to blood smears. Finally, ektacytometry's ability to detect deformability of erythrocytes in NA seems to depend on the degree of acanthocytosis.

Dataset Information

Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.

Background

Case presentation

Conclusion

Publications

Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.

Similar Datasets

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