Clinical and molecular genetic assessment of a chorea-acanthocytosis pedigree.
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.
Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
Mio
M
Ichiba
Masayuki
M
Nakamura
Akira
A
Kusumoto
Emiko
E
Mizuno
Yutaka
Y
Kurano
Mieko
M
Matsuda
Maiko
M
Kato
Asumi
A
Agemura
Yuko
Y
Tomemori
Shinji
S
Muroya
Yoshiaki
Y
Nakabeppu
Akira
A
Sano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D054546:Neuroacanthocytosis / Q000235:genetics* / Q000503:physiopathology; D009483:Neuropsychological Tests; D010375:Pedigree; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D033921:Vesicular Transport Proteins / Q000235:genetics*
D012333:RNA, Messenger; C429654:VPS13A protein, human; D033921:Vesicular Transport Proteins