Genotype-phenotype correlates in Taiwanese patients with early-onset recessive Parkinsonism.
We screened for mutations in the PARKIN, DJ-1, and PINK1 genes in a Taiwanese cohort (68 probands; 58 sporadic and 10 familial) with early-onset parkinsonism (EOP, onset <50 years of age). We identified 9 patients harboring mutations in PARKIN (three compound heterozygous and six single heterozygous carriers), 3 patients with heterozygous PINK1 mutations (including two novel substitutions M341I and P209A), and no DJ-1 mutations. Our frequencies of PARKIN (two allele mutation, 4.4%; single allele, 8.8%) and PINK1 (single heterozygous, 4.4%) mutations in Taiwanese-Chinese are similar to those in Caucasian and other Asian EOP patients. Although the role of heterozygosity of recessive genes in EOP remains to be resolved, molecular analysis and functional imaging will play a decisive role in differential diagnosis and determined therapeutic strategy.
Lee
Ming-Jen
MJ
Department of Medical Genetics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Mata
Ignacio F
IF
Lin
Chin-Hsien
CH
Tzen
Kai-Yuan
KY
Lincoln
Sarah J
SJ
Bounds
Rebecca
R
Lockhart
Paul J
PJ
Hulihan
Mary M
MM
Farrer
Matthew J
MJ
Wu
Ruey-Meei
RM
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D002681:China / Q000208:ethnology; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015513:Oncogene Proteins / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000208:ethnology* / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human