OBJECTIVE: To explore the clinical characteristics and genetic variants in a child with tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay. METHODS: Clinical feature of the patient was summarized. Genomic DNA was extracted from peripheral blood samples taken from the child and her family members. All exons of GCH1, TH and SPR genes were subjected to targeted capture and next-generation sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The child could not sit alone at 7 month and 11 days. Physical examination suggested motor retardation and hypotonia, limb stiffness, head nodding, slight torticollis, and language and intellectual developmental delays. She developed involuntary shaking of limbs at 3 month old, which lasted approximately 10 seconds and aggregated with excitement and before sleeping. Cranial MRI revealed widening of subarachnoid space on the temporomandibular and particularly temporal sides. Genetic testing revealed that she has carried a nonsense c.457C>T (p.R153X) variant, which was known to be pathogenic, and a novel missense c.720C>G (p.I240M) variant of the TH gene. The two variants were derived from her father and mother, respectively. CONCLUSION The child was diagnosed as tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay due to compound heterozygous variants of the TH gene. Above finding has enriched the spectrum of TH gene variants.
Brain ; diagnostic imaging ; Codon, Nonsense ; Dystonic Disorders ; congenital ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Magnetic Resonance Imaging ; Mutation ; Parkinsonian Disorders ; genetics ; Tyrosine 3-Monooxygenase ; genetics

The traditionally used oriental herbal medicine Moutan Cortex Radicis [MCR; Paeonia Suffruticosa Andrews (Paeoniaceae)] exerts anti-inflammatory, anti-spasmodic, and analgesic effects. In the present study, we investigated the therapeutic effects of differently fractioned MCR extracts in a 6-hydroxydopamine (OHDA)-induced Parkinson's disease model and neuro-blastoma B65 cells. Ethanol-extracted MCR was fractionated by n-hexane, butanol, and distilled water. Adult Sprague-Dawley rats were treated first with 20 μg of 6-OHDA, followed by three MCR extract fractions (100 or 200 mg·kg) for 14 consecutive days. In the behavioral rotation experiment, the MCR extract-treated groups showed significantly decreased number of net turns compared with the 6-OHDA control group. The three fractions also significantly inhibited the reduction in tyrosine hydroxylase-positive cells in the substantia nigra pars compacta following 6-OHDA neurotoxicity. Western blotting analysis revealed significantly reduced tyrosine hydroxylase expression in the substantia nigra pars compacta in the 6-OHDA-treated group, which was significantly inhibited by the n-hexane or distilled water fractions of MCR. B65 cells were exposed to the extract fractions for 24 h prior to addition of 6-OHDA for 30 min; treatment with n-hexane or distilled water fractions of MCR reduced apoptotic cell death induced by 6-OHDA neurotoxicity and inhibited nitric oxide production and neuronal nitric oxide synthase expression. These results showed that n-hexane- and distilled water-fractioned MCR extracts inhibited 6-OHDA-induced neurotoxicity by suppressing nitric oxide production and neuronal nitric oxide synthase activity, suggesting that MCR extracts could serve as a novel candidate treatment for the patients with Parkinson's disease.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Antiparkinson Agents ; pharmacology ; therapeutic use ; Cell Death ; drug effects ; Cell Line ; Disease Models, Animal ; Drugs, Chinese Herbal ; chemistry ; Neurons ; pathology ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type I ; biosynthesis ; Oxidopamine ; toxicity ; Paeonia ; chemistry ; Parkinsonian Disorders ; chemically induced ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plants, Medicinal ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; enzymology ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

OBJECTIVETo investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms.

METHODSClinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing.

RESULTSThe symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives.

CONCLUSIONCADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.

Alopecia ; etiology ; CADASIL ; complications ; diagnostic imaging ; genetics ; Humans ; Low Back Pain ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; Parkinsonian Disorders ; etiology ; Receptor, Notch3 ; genetics

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.
Adult ; Aged ; Brain/*radionuclide imaging ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Male ; Middle Aged ; Organotechnetium Compounds/diagnostic use ; Paraplegia/diagnosis/genetics/*radionuclide imaging ; Parkinsonian Disorders/complications/genetics/*radionuclide imaging ; Pyramidal Tracts ; Radiopharmaceuticals/diagnostic use ; Spastic Paraplegia, Hereditary/diagnosis/genetics/*radionuclide imaging ; Tomography, Emission-Computed, Single-Photon

Adolescent ; Adult ; DNA ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Male ; Mutation ; Parkinsonian Disorders ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics

BACKGROUNDParkinson's disease (PD) is an autosomally inherited neurodegenerative disease in elderly people. The etiology of PD has long been thought to be associated with both genetic and environmental factors. To explore potential genetic risk factors for PD in the northern Han Chinese population, we investigated three single nucleotide polymorphisms (SNPs) (rs4538475, rs11107 and rs12564040) in the BST1, PARK15 and PARK9 genes.

METHODSGenomic DNA from 215 PD patients and 212 matched controls was amplified in two independent PCR systems and subsequently genotyped by digestion with the endonuclease PstI. Genetic parameter and association studies were carried out with SPSS 13.0 and PLINK 1.07 software.

RESULTSWe could accurately detect all genotypes in the three loci with the PCR-RFLP or mismatched PCR-RFLP techniques. The observed heterozygosities of the rs4538475 and rs11107 loci in PD and control groups ranged from 0.460 - 0.481 and 0.410 - 0.441, in BST1, PARK15 respectively, while we detected no heterozygosity at the rs12564040 locus in PARK9. The similar distributions of genotypic frequency between both groups suggest that the three SNPs investigated in this study are unlikely to play roles as common risk factors or pathogenic mutations for PD in northern Han Chinese.

CONCLUSIONThe SNPs investigated in the BST1, PARK15 and PARK9 genes associated with PD susceptibility are not associated with PD in the northern Han Chinese population.

ADP-ribosyl Cyclase ; genetics ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; genetics ; Asian Continental Ancestry Group ; genetics ; F-Box Proteins ; genetics ; Female ; GPI-Linked Proteins ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Parkinsonian Disorders ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; genetics ; Young Adult

OBJECTIVETo establish a method for analyzing the PTEN-induced kinase 1 gene (PINK1) exon copy number and apply it to the analysis of PINK1 gene exon copy number variation (CNV) in patients with autosomal recessive early-onset Parkinsonism (AREP).

METHODSReal-time PCR was used to analyze the exon copy number in 22 probands with AREP from unrelated Chinese Han families and 30 healthy controls.

RESULTSCopy numbers of exons 1-8 of the PINK1 gene were analyzed, and satisfactory reaction conditions and primers for exons of the PINK1 gene were obtained. No exon CNV in the PINK1 gene was detected in this group.

CONCLUSIONAn analytical method for PINK1 gene exon copy number was established. The exon CNV in the PINK1 gene was rare in Chinese patients with AREP.

Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; Exons ; genetics ; Female ; Gene Dosage ; genetics ; Humans ; Male ; Parkinsonian Disorders ; genetics ; Polymerase Chain Reaction ; methods ; Protein Kinases ; genetics ; Young Adult

OBJECTIVE: To establish a technique platform of DJ-1 gene exon rearrangement using real-time PCR and to analyze DJ-1 gene exon rearrangement mutation in patients with autosomal recessive early-onset Parkinsonism(AREP). METHODS: Real-time PCR was used to analyze DJ-1 gene exon rearrangement mutation in 22 probands with AREP from unrelated Chinese Han families and 30 normal controls. RESULTS: We obtained satisfactory real-time PCR reaction conditions and primers of DJ-1 gene coding exons No exon rearrangement mutation in the DJ-1 gene is detected in this group. CONCLUSION We established platform of DJ-1 gene exon rearrangement using real-time PCR. Exon rearrangement mutation in the DJ-1 gene is rare in Chinese patients with AREP.
Adolescent ; Adult ; Age of Onset ; Child ; Child, Preschool ; China ; ethnology ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Gene Rearrangement ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Mutation ; Oncogene Proteins ; genetics ; Parkinsonian Disorders ; genetics ; Protein Deglycase DJ-1 ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

OBJECTIVETo investigate the mutation characteristics of ATP13A2 gene in Chinese patients with familial autosomal recessive early-onset parkinsonism (AREP).

METHODSMutations of ATP13A2 gene were screened by polymerase chain reaction combined with DNA direct sequencing in patients with familial AREP.

RESULTSNo pathogenic mutations in ATP13A2 gene were detected in this group. Six reported polymorphisms were identified. They were IVS6+70A>G, IVS12+66A>G, m.1849C>T, IVS20-56 G>A, m2671C>T and m2824G>A.

CONCLUSIONATP13A2 gene mutations may be rare in Chinese patients with familial autosomal recessive early-onset parkinsonism.

Adult ; Age of Onset ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; epidemiology ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Parkinsonian Disorders ; epidemiology ; genetics ; Pedigree ; Polymorphism, Genetic ; Proton-Translocating ATPases ; genetics

Adult ; Asian Continental Ancestry Group ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Parkinsonian Disorders ; genetics ; Pedigree ; Proton-Translocating ATPases ; genetics ; Young Adult