High frequency of Parkin exon rearrangements in Mexican-mestizo patients with early-onset Parkinson's disease.
BACKGROUND
Parkin mutations in patients with early-onset Parkinson's disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases.


METHODS
We analyzed the entire sequence-coding region and dosage mutations of parkin in 63 Mexican-mestizo EOPD patients and 120 controls.


RESULTS
Parkin mutations were present in 34 patients (54.0%). Exon rearrangements, predominantly spanning exons 9 and 12 (31.7% and 19.0%, respectively) were present in 32 patients, with 17.5% carrying simple heterozygous and 25.4% carrying compound heterozygous parkin mutations.


CONCLUSIONS
A higher frequency of parkin exon rearrangements than of sequence mutations was observed. Patients with parkin exons 9 and 12 rearrangements showed a later age at onset than did cases with other regions affected (40.3 ± 4.5 vs 30.1 ± 8.8; P = .005), suggesting a mutational hot spot in the etiology of Mexican-mestizo patients with EOPD. To our knowledge, this study represents the largest sampling of Mexican-mestizo patients with EOPD cases for which parkin sequence and dosage alterations were analyzed. .
Neurogenetics Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.
Jorge Luis
JL
Guerrero Camacho
Nancy
N
Monroy Jaramillo
Petra
P
Yescas Gómez
Mayela
M
Rodríguez Violante
Catherine
C
Boll Woehrlen
Ma Elisa
ME
Alonso Vilatela
Marisol
M
López López
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005787:Gene Frequency; D015321:Gene Rearrangement; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D014202:Tremor / Q000209:etiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein