Clinical and molecular genetic assessment of a chorea-acanthocytosis pedigree
Mio Ichiba1, Masayuki Nakamura, Akira Kusumoto
1Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
Insights
Chorea-acanthocytosis (ChAc) carriers may exhibit neurological symptoms. This study followed a ChAc patient and their family, revealing potential heterozygous VPS13A mutation effects.
Area of Science:
- Neurogenetics
- Neurodegenerative Diseases
Background:
- Chorea-acanthocytosis (ChAc) is an autosomal recessive disorder.
- It is caused by VPS13A gene mutations, leading to striatal neurodegeneration and acanthocytosis.
- Limited data exists on the clinical status of ChAc carriers.
Purpose of the Study:
- To investigate the clinical, radiological, and neuropsychological progression of a Chorea-acanthocytosis patient.
- To evaluate the clinical features of ChAc family members, including heterozygous carriers.
Main Methods:
- A Chorea-acanthocytosis index patient and their pedigree were followed.
- Clinical features were assessed, alongside genetic analyses of VPS13A and other relevant genes.
- Neuropsychological evaluations and brain imaging were conducted over three years.
Main Results:
- The index patient was homozygous for a VPS13A mutation, presenting a typical ChAc phenotype.
- Progressive basal ganglia and frontal lobe atrophy, reduced blood flow, and cognitive decline were observed in the patient.
- Four of five heterozygous carriers showed symptoms potentially linked to the VPS13A mutation.
Conclusions:
- VPS13A mutations can lead to progressive neurodegeneration and cognitive impairment in Chorea-acanthocytosis patients.
- Heterozygous carriers of VPS13A mutations may exhibit clinical signs and symptoms.
- Further research is needed to understand the full spectrum of ChAc and carrier phenotypes.
Background:
Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis that is caused by mutations in the VPS13A gene. There are only few reports that studied clinical status of the obligate carriers of ChAc. Clinical courses with follow-up neuroradiological and neuropsychological evaluations in individuals with ChAc have been rarely reported.
Methods:
We followed an index patient with ChAc and evaluated the clinical features of the pedigree members. Genetic analyses of VPS13A and genes responsible for other neuroacanthocytotic and neurodegenerative diseases were performed.
Conclusions:
The index patient was homozygous for a 3889C>T nonsense mutation in the VPS13A gene and presented with a typical ChAc phenotype. Neuropsychological evaluation with brain imaging in the patient over 3 years revealed atrophy and a decrease in blood flow at the basal ganglia and frontal lobe, and impairment in cognitive function reflecting frontal lobe dysfunction in progressive manners. Four out of five heterozygous mutation carriers in the pedigree showed signs or symptoms potentially attributable to a heterozygous VPS13A mutation.
More Related Videos
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
Related Concept Videos
01:35Pedigree Analysis
01:35Pedigree Analysis
02:59Animal Mitochondrial Genetics
01:21Huntington Disease l: Introduction
01:17Karyotyping
01:17Karyotyping