Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

Autor: Monroy-Jaramillo N; Neurogenetics Department, National Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez', Mexico City, Mexico; PhD Candidate in Biological and Health Sciences, Universidad Autónoma Metropolitana, Mexico City, Mexico., Guerrero-Camacho JL, Rodríguez-Violante M, Boll-Woehrlen MC, Yescas-Gómez P, Alonso-Vilatela ME, López-López M
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2014 Apr; Vol. 165B (3), pp. 235-44. Date of Electronic Publication: 2014 Feb 23.
DOI: 10.1002/ajmg.b.32228
Abstrakt: Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.
(© 2014 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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