OBJECTIVETo investigate the gene mutations and the clinical features of Chinese patients with autosomal recessive juvenile parkinsonism(AR-JP).

METHODSthe polymerase chain reaction (PCR), DNA sequence analysis, and restriction enzyme digestion analysis were applied to check parkin gene mutations of 15 index patients from 15 families with AR-JP.

RESULTSThree families were detected to have parkin mutations. Two of them had heterozygous deletion mutations (202-203 del AG in exon 2, 1069-1074 del GTGTCC in exon 9) and another of them carried a heterozygous missense mutation [1422(T-->C) in exon 12]. Two of the mutations [1069-1074delGTGTCC and 1422(T-->C)] were not reported previously. There were six patients in the three families. Mean age at onset was 25.2+/-5.7 years, ranging from 18 to 31 years. The symptoms were under slow progression, diurnal fluctuation with sleep benefit, and hyperreflexia were relatively prominent. Response to levodopa was satisfactory.

CONCLUSIONThere are parkin mutations happened in Chinese patients with AR-JP. Patients with parkin mutations have distinct clinical features besides the common clinical features of Parkinson's disease.

Adult ; Family Health ; Female ; Gene Deletion ; Genotype ; Humans ; Male ; Mutation ; Parkinsonian Disorders ; genetics ; Phenotype ; Ubiquitin-Protein Ligases ; genetics

The gene responsible for autosomal recessive parkinsonism, parkin, has recently been identified on chromosome 6q. It has been shown to be mutated in Japanese and European families, most of whom had early-onset parkinsonism. Here, we present a family with young-onset parkinsonism of an autosomal recessive inheritance. A homozygous exon 4 deletion in the parkin gene was found in 3 family members. To the best of the authors' knowledge, this is the first report in Korea of familial parkinsonism with the parkin gene mutation.
*Exons ; Female ; *Gene Deletion ; Genes, Recessive ; Human ; Ligases/*genetics ; Middle Aged ; Parkinsonian Disorders/*genetics ; *Ubiquitin-Protein Ligases

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

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

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

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

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

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

OBJECTIVETo investigate the mutation characteristics of DJ1 gene in Chinese patients with autosomal recessive early-onset Parkinsonism (AR-EP).

METHODSMutations of DJ1 gene were screened by polymerase chain reaction combined with DNA direct sequencing in index patients with AR-EP from 11 unrelated families.

RESULTSNo pathogenetic mutations in the DJ1 gene were detected in this group. Six intronic DJ1 polymorphisms (IVS1-15T-->C, IVS4+30T-->G, IVS4+45G-->A, IVS4+46G-->A, IVS5+31G-->A, g.168-185del) were found. Three of them (IVS1-15T-->C, IVS4+45G-->A, IVS4+46G-->A) were not reported previously.

CONCLUSIONDJ1 mutations were rare in Chinese patients with autosomal recessive early-onset Parkinsonism.

Adolescent ; Adult ; Age of Onset ; Base Sequence ; China ; epidemiology ; DNA Mutational Analysis ; methods ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Oncogene Proteins ; genetics ; Parkinsonian Disorders ; epidemiology ; genetics ; Polymerase Chain Reaction ; Protein Deglycase DJ-1 ; Young Adult

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