𝔖 Bobbio Scriptorium
✦   LIBER   ✦

GCH1 in early-onset Parkinson's disease

✍ Scribed by Stephanie A. Cobb; Christian Wider; Owen A. Ross; Ignacio F. Mata; Charles H. Adler; Alex Rajput; Ali H. Rajput; Ruey-Meei Wu; Robert Hauser; Keith A. Josephs; Jonathan Carr; Katrina Gwinn; Michael G. Heckman; Jan O. Aasly; Timothy Lynch; Ryan J. Uitti; Zbigniew K. Wszolek; Gregory Kapatos; Matthew J. Farrer

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
95 KB
Volume
24
Category
Article
ISSN
0885-3185

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Mutations in GTP‐cyclohydrolase 1 (GCH1) cause autosomal dominant dopa‐responsive dystonia (DRD), characterized by childhood‐onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early‐onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ‐1. In addition, we examined a matched EOPD patient–control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy‐number abnormality was identified in familial EOPD patients. A novel 18‐bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN‐positive patients were 10 years younger than PRKN‐negative patients and had a twofold higher prevalence of dystonia. This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD. © 2009 Movement Disorder Society

📜 SIMILAR VOLUMES

PINK1 mutations in sporadic early-onset
PINK1 mutations in sporadic early-onset Parkinson's disease
✍ Eng-King Tan; Kenneth Yew; Eva Chua; K. Puvan; Hui Shen; Esther Lee; Kim-Yoong P 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 347 KB 👁 1 views

## Abstract Pathogenic __PINK1__ mutations have been described in PARK6‐linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of __PINK1__ mutations in sporadic early‐onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to

The PLA2G6 gene in early-onset Parkinson
The PLA2G6 gene in early-onset Parkinson's disease
✍ Kai Michael Kauther; Christine Höft; Ida Rissling; Wolfgang H. Oertel; Jens Cars 📂 Article 📅 2011 🏛 John Wiley and Sons 🌐 English ⚖ 313 KB

## Abstract ## Background: The definite etiology of neurodegenerative disorders such as Parkinson's disease (PD) is still unknown. Because of its role in the generation of reactive oxygen species and its association with neurodegeneration with brain iron accumulation, a possible involvement of cal

PINK1 mutations in a Brazilian cohort of
PINK1 mutations in a Brazilian cohort of early-onset Parkinson's disease patients
✍ Clecio Godeiro-Junior; Patricia M. de Carvalho-Aguiar; Andre C. Felício; Orlando 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 218 KB 👁 1 views

## Abstract Data on the frequency of __PINK1__ mutations in Brazilian patients with early‐onset Parkinson's disease (EOPD) are lacking. The aim of this report was to investigate mutations of the __PINK1__ gene in a cohort of Brazilian patients with EOPD. Sixty consecutive familial or sporadic EOPD

Familial aggregation of early- and late-
Familial aggregation of early- and late-onset Parkinson's disease
✍ Karen Marder; Gilberto Levy; Elan D. Louis; Helen Mejia-Santana; Lucien Cote; Ho 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 91 KB 👁 2 views

The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the f

Recurrent LRRK2 (Park8) mutations in ear
Recurrent LRRK2 (Park8) mutations in early-onset Parkinson's disease
✍ Katja Hedrich; Susen Winkler; Johann Hagenah; Kemal Kabakci; Meike Kasten; Eberh 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 95 KB 👁 1 views

## Abstract Mutations in __LRRK2__ (__leucine‐rich repeat kinase 2__) have been associated with autosomal dominant Parkinson's disease (PD) and cluster in several 3′ exons of the gene. The majority of mutations have been detected in late‐onset cases (age at onset >50 years). We screened 5 of the 51