You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


ABOUT ARCHIVES
Advanced Search

Welcome   | My Account | E-mail Alerts | Access Rights | Sign In


  Vol. 59 No. 6, June 2002 TABLE OF CONTENTS
  Archives
  •  Online Features
  Original Contribution
 This Article
 •Full text
 •PDF
 • Reply to article
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on ISI (24)
 •Contact me when this article is cited
 Related Content
 •Related article
 •Similar articles in this journal
 Topic Collections
 •Neurogenetics
 •Movement Disorders
 •Parkinson Disease/ Parkinsonian Disorders
 •Genetic Counseling/ Testing/ Therapy
 •Genetic Disorders
 •Alert me on articles by topic

Molecular Findings in Familial Parkinson Disease in Spain

Janet Hoenicka, PhD; Lídice Vidal, BS; Blas Morales, MD, PhD; Israel Ampuero, BS; F. Javier Jiménez-Jiménez, MD, PhD; Jose Berciano, MD, PhD; Teodoro del Ser, MD, PhD; Adriano Jiménez, MD, PhD; Pedro G. Ruíz, MD, PhD; Justo G. de Yébenes, MD, PhD

Arch Neurol. 2002;59:966-970.

Background  Several genetic errors in {alpha}-synuclein (Park1) and ubiquitin carboxyl-terminal–hydrolase L1(Park5) genes cause autosomal dominant familial Parkinson disease. Mutations in the parkin gene (Park2) are the major cause of autosomal recessive Parkinson disease.

Objective  To analyze the clinical and molecular data of 19 Spanish kindreds (13 with recessive, 4 with dominant, and 2 with uncertain inheritance) who have familial Parkinson disease.

Methods  We searched for the previously described mutations in Park1 and Park5 genes and for new or described mutations in Park2. We used single-strand conformation polymorphism, direct sequencing, and restriction digestion of polymerase chain reaction (PCR)–amplified genomic DNA for this study.

Results  None of these families have either Park1 or Park5 mutations. We found 5 different mutations in Park2 gene in 5 of the families with recessive inheritance. To our knowledge, 2 of these mutations, V56E and C212Y, have not been previously reported. The other mutations found (deletion of exons 3 and 5 and 225delA) have been described in other ethnic groups. Heterozygous carriers of a single Park2 mutation either were asymptomatic or developed clinical symptoms in late adulthood or after brief exposure to haloperidol therapy.

Conclusions  Mutations in Park2 gene account for 38% of the families with recessive parkinsonism in Spain. We found 2 cases of simple heterozygous Park2 mutation carriers that developed clinical symptoms, either in late adulthood or after brief exposure to parkinsonizing agents. Thus, hereditary Parkinson disease has more variable clinical phenotype and molecular defects than previously thought since heterozygous mutations could be a risk factor for parkinsonism.


From the Unidad de Diagnóstico Molecular, Banco de Tejidos para Investigaciones Neurológicas, Madrid (Drs Hoenicka and de Yébenes, Ms Vidal, and Mr Ampuero), Servicios de Neurología, Hospital Universitario S Cecilio, Granada (Dr Morales), Hospital Príncipe de Asturias, Alcalá de Henares (Dr Jiménez-Jiménez), Hospital Severo Ochoa, Leganés (Dr del Ser), Hospital Ramón y Cajal, Madrid, and Hospital Marqués de Valdecilla, Cantabria (Dr Jiménez), and Fundación Jiménez Díaz, Madrid (Drs Berciano, Ruíz, and de Yébenes), Spain.


RELATED ARTICLE

Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2002;59(6):1048-1050.
FULL TEXT  






HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 2002 American Medical Association. All Rights Reserved.