𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease

✍ Scribed by Jan O. Aasly; Carles Vilariño-Güell; Justus C. Dachsel; Philip J. Webber; Andrew B. West; Kristoffer Haugarvoll; Krisztina K. Johansen; Mathias Toft; John G. Nutt; Haydeh Payami; Jennifer M. Kachergus; Sarah J. Lincoln; Amela Felic; Christian Wider; Alexandra I. Soto-Ortolaza; Stephanie A. Cobb; Linda R. White; Owen A. Ross; Matthew J. Farrer

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
608 KB
Volume
25
Category
Article
ISSN
0885-3185

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Genealogical investigation of a large Norwegian family (F04) with autosomal dominant parkinsonism has identified 18 affected family members over four generations. Genetic studies have revealed a novel pathogenic LRRK2 mutation c.4309 A>C (p.Asn1437His) that co‐segregates with disease manifestation (LOD = 3.15, θ = 0). Affected carriers have an early age at onset (48 ± 7.7 SD years) and are clinically asymmetric and levodopa responsive. The variant was absent in 623 Norwegian control subjects. Further screening of patients from the same population identified one additional affected carrier (1 of 692) with familial parkinsonism who shares the same haplotype. The mutation is located within the Roc domain of the protein and enhances GTP‐binding and kinase activity, further implicating these activities as the mechanisms that underlie LRRK2‐linked parkinsonism. © 2010 Movement Disorder Society

📜 SIMILAR VOLUMES

Pathogenicity of LRRK2 P755L variant in
Pathogenicity of LRRK2 P755L variant in Parkinson's disease
✍ Eng-King Tan; Hui-Qin Lim; Yih Yuen; Yi Zhao 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 173 KB

## Abstract A heterozygous 2264C→T variant (P755L) in __LRRK2__ gene has been reported to be a likely pathogenic variant among ethnic Chinese patients with Parkinson's disease (PD). In a case control study, we performed genetic analysis of the P755L variant in an independent cohort of Chinese patie

Pathogenicity of the Lrrk2 R1514Q substi
Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease
✍ Mathias Toft; Ignacio F. Mata; Owen A. Ross; Jennifer Kachergus; Mary M. Hulihan 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 92 KB

## Abstract An increasing number of nonsynonymous __LRRK2__ variants are being reported as putative pathogenic mutations. We identified one large kindred harboring the Lrrk2 R1514Q substitution; however, the variant did not segregate fully with disease. Combined analyses of three case–control serie

R1514Q substitution in Lrrk2 is not a pa
R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation
✍ William C. Nichols; Diane K. Marek; Michael W. Pauciulo; Nathan Pankratz; Cheryl 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 66 KB

## Abstract Mutations in __LRRK2__ were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen __LRRK2__ substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A)

G2019S LRRK2 mutation in familial and sp
G2019S LRRK2 mutation in familial and sporadic Parkinson's disease in Russia
✍ Sofya N. Pchelina; Andrei F. Yakimovskii; Olga N. Ivanova; Anton K. Emelianov; A 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 80 KB

## Abstract Among mutations associated with autosomal dominant and sporadic Parkinson's disease (PD) the G2019S substitution in the leucine‐rich repeat kinase 2 (LRRK2) gene is the most frequently identified. To estimate its frequency in Russia, we analyzed 208 patients with PD from the Northwester

LRRK2 haplotype-sharing analysis in Park
LRRK2 haplotype-sharing analysis in Parkinson's disease reveals a novel p.S1761R mutation
✍ Oswaldo Lorenzo-Betancor; Lluís Samaranch; Mario Ezquerra; Eduardo Tolosa; Elena 📂 Article 📅 2011 🏛 John Wiley and Sons 🌐 English ⚖ 1006 KB

## Abstract ## Background and objective. Mutations in the __Leucine‐Rich Repeat Kinase 2__ (__LRRK2__) gene at chromosome 12q12 are the most common genetic cause of sporadic and familial late‐onset Parkinson's disease. Our aim was to identify novel __LRRK2__ mutations in late‐onset Parkinson's dis

High prevalence of LRRK2 mutations in fa
High prevalence of LRRK2 mutations in familial and sporadic Parkinson's disease in Portugal
✍ Joaquim J. Ferreira; Leonor Correia Guedes; Mário Miguel Rosa; Miguel Coelho; Ma 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 122 KB 👁 1 views

## Abstract Mutations in the __Leucine‐Rich Repeat Kinase 2__ (__LRRK2__) gene are the most frequent known cause of Parkinson's disease (PD), but their prevalence varies markedly between populations. Here we studied the frequency and associated phenotype of four recurrent __LRRK2__ mutations (R1441