Novel pathogenic mutations and copy number variations in the VPS13A gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc.

PLA2G6 variants associated with the number of affected alleles in Parkinson's disease in Japan.

This study aimed to evaluate genotype-phenotype correlations of Parkinson's disease (PD) patients with phospholipase A2 group V (PLA2G6) variants. We analyzed the DNA of 798 patients with PD, including 78 PD patients reported previously, and 336 in-house controls. We screened the exons and exon-intron boundaries of PLA2G6 using the Ion Torrent system and Sanger method. We identified 21 patients with 18 rare variants, such that 1, 9, and 11 patients were homozygous, heterozygous, and compound heterozygous, respectively, with respect to PLA2G6 variants. The allele frequency was approximately equal between patients with familial PD and those with sporadic PD. The PLA2G6 variants detected frequently were identified in the early-onset sporadic PD group. Patients who were homozygous for a variant showed more severe symptoms than those who were heterozygous for the variant. The most common variant was p.R635Q in our cohort, which was considered a risk variant for PD. Thus, the variants of PLA2G6 may play a role in familial PD and early-onset sporadic PD.

A case of Parkinson's disease following dystonia.

Parkinsonism and dystonia are both disorders of the extrapyramidal motor system, and some patients exhibit a complex of the two symptoms. Although several reports have referred to the coexistence of these disorders as parkinsonian disorders with dystonia, in the majority of cases, dystonia appeared after parkinsonism. DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other types of parkinsonism such as dementia with Lewy bodies. This case report describes a 67-year old woman diagnosed with axial dystonia without parkinsonism 6 years previously, which had worsened despite treatment with Botulinum toxin injections, and hindered the patient's gait. The patient visited the hospital because of gait disturbances and DAT-scan showed a levodopa transducer decrease in the putamen. A few weeks later, she was re-admitted to hospital and exhibited Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this was a rare case of parkinsonian disorders with dystonia, characterized by the development of PD after dystonia. DAT-scan may be helpful for the diagnosis of patients with parkinsonian disorders with dystonia.