Novel parkin mutations detected in patients with early-onset Parkinson's disease.
نویسندگان
چکیده
A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.
منابع مشابه
Parkin (PARK 2) Mutations Are Rare in Czech Patients with Early-Onset Parkinson's Disease
OBJECTIVE The aim of the study is to determine the frequency of parkin allelic variants in Czech early-onset Parkinson's disease patients and healthy controls. METHODS A total of 70 early-onset Parkinson's disease patients (age at onset ≤40 years) and 75 controls were screened for the sequence variants and exon rearrangements in the parkin gene. RESULTS Parkin mutations were identified in f...
متن کاملMutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa.
Parkinson's disease is a frequent disorder caused primarily by the loss of dopaminergic neurons of the substantia nigra. Mutations in the PTEN-induced kinase (PINK1) gene, in addition to those in parkin and DJ-1, have been found in families with recessive early-onset Parkinson's disease. We screened for parkin and PINK1 mutations in a panel of 177 autosomal recessive Parkinson's disease familie...
متن کاملMutational screening of the parkin gene among South Indians with early onset Parkinson's disease.
Parkin mutations are commonly encountered in multiethnic populations with familial early onset Parkinson's disease (PD) and less frequently in sporadic PD. A total of 102 patients (recruited from a hospital) with early onset PD from an ethnically homogeneous Indian population (age of onset < or =50 years) including both familial (n = 20) and sporadic (n = 82) cases were screened for parkin muta...
متن کاملRelative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism.
BACKGROUND Autosomal recessive juvenile parkinsonism is a neurodegenerative disorder associated with mutations in the parkin gene. OBJECTIVES To search for the presence of parkin gene mutations in Spanish patients with Parkinson's disease (PD) and characterise the phenotype associated with these mutations. METHODS Thirty seven PD patients with either early onset or autosomal recessive patte...
متن کاملGenotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < or = 50 years) were phenotyped and screened for mutations in...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Movement disorders : official journal of the Movement Disorder Society
دوره 20 4 شماره
صفحات -
تاریخ انتشار 2005