PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations.
Mov Disord
; 26(1): 80-9, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21322020
ABSTRACT
We present results of mutation screening of PRKN gene in 93 Iranian Parkinson's disease (PD) patients with average age at onset (AAO) of 42.2 years. The gene was screened by direct sequencing and by a semi-quantitative PCR protocol for detection of sequence rearrangements. Heterozygous rearrangements were tested by reverse transcription-polymerase chain reaction (RT-PCR). Nine different PRKN mutations were found. One of these, IVS9+1G>A, affects splicing and is novel. Two mutated PRKN alleles were observed in each of 6 patients whose average AAO was 25.7 years. Only 1 patient carried a single mutated allele and his AAO was 41 years. Among patients with AAO of <30 years, 31.3% had two mutated alleles, while only 2.6% with AAO of >30 years carried a PRKN mutation. Analysis of PRKN by RT-PCR led to identification of a novel exon expressed in leukocytes of control and PD individuals. The alternatively spliced transcript if translated would code a protein without a RING Finger 2 domain. Its functional relevance remains to be shown. DJ-I and PINK1 were also screened. Two novel DJ-1 mutations, c.91-2A>G affecting splicing and c.319G>C causing Ala107Pro, were observed among patients with AAO of <31 years, suggesting that PD in a high fraction (>12%) of this group of Iranian patients may be due to mutations in DJ-1. Mutations in PINK1 were not observed. Our results complement previous findings on LRRK2 mutations among Iranian PD patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Proteínas Quinases
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Proteínas Oncogênicas
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Predisposição Genética para Doença
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Ubiquitina-Proteína Ligases
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Peptídeos e Proteínas de Sinalização Intracelular
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Limite:
Adolescent
/
Adult
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Aged
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Child
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Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article