A susceptibility locus for Parkinson's disease maps to chromosome 2p13

T. Gasser, B. Muller-Myhsok, Z. K. Wszolek, R. Oehlmann, D. B. Calne, V. Bonifati, B. Bereznai, E. Fabrizio, P. Vieregge, R. D. Horstmann

Research output: Article

429 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease. Firstly, clinico- genetic, epidemiologic and twin studies revealed inheritable effects and questioned earlier studies which had denied such influences. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically and in some cases also neuropathologically. Recently, a disease locus has been mapped to chromosome 4q21-22 in a large Mediterranean pedigree, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease- causing mutation has been identified in the gene encoding α-synuclein. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the α-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40%. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.

Original languageEnglish
Pages (from-to)262-265
Number of pages4
JournalNature Genetics
Volume18
Issue number3
DOIs
Publication statusPublished - 1998

Fingerprint

Parkinson Disease
Chromosomes
Synucleins
Parkinsonian Disorders
Age of Onset
Mutation
Lewy Bodies
Chromosomes, Human, Pair 22
Twin Studies
Genetic Loci
Genetic Heterogeneity
Penetrance
Dopaminergic Neurons
Pedigree
Neurodegenerative Diseases
Epidemiologic Studies
Brain
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gasser, T., Muller-Myhsok, B., Wszolek, Z. K., Oehlmann, R., Calne, D. B., Bonifati, V., ... Horstmann, R. D. (1998). A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nature Genetics, 18(3), 262-265. https://doi.org/10.1038/ng0398-262

A susceptibility locus for Parkinson's disease maps to chromosome 2p13. / Gasser, T.; Muller-Myhsok, B.; Wszolek, Z. K.; Oehlmann, R.; Calne, D. B.; Bonifati, V.; Bereznai, B.; Fabrizio, E.; Vieregge, P.; Horstmann, R. D.

In: Nature Genetics, Vol. 18, No. 3, 1998, p. 262-265.

Research output: Article

Gasser, T, Muller-Myhsok, B, Wszolek, ZK, Oehlmann, R, Calne, DB, Bonifati, V, Bereznai, B, Fabrizio, E, Vieregge, P & Horstmann, RD 1998, 'A susceptibility locus for Parkinson's disease maps to chromosome 2p13', Nature Genetics, vol. 18, no. 3, pp. 262-265. https://doi.org/10.1038/ng0398-262
Gasser T, Muller-Myhsok B, Wszolek ZK, Oehlmann R, Calne DB, Bonifati V et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nature Genetics. 1998;18(3):262-265. https://doi.org/10.1038/ng0398-262
Gasser, T. ; Muller-Myhsok, B. ; Wszolek, Z. K. ; Oehlmann, R. ; Calne, D. B. ; Bonifati, V. ; Bereznai, B. ; Fabrizio, E. ; Vieregge, P. ; Horstmann, R. D. / A susceptibility locus for Parkinson's disease maps to chromosome 2p13. In: Nature Genetics. 1998 ; Vol. 18, No. 3. pp. 262-265.
@article{047066ec304f48658ac3f73abce8836f,
title = "A susceptibility locus for Parkinson's disease maps to chromosome 2p13",
abstract = "Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease. Firstly, clinico- genetic, epidemiologic and twin studies revealed inheritable effects and questioned earlier studies which had denied such influences. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically and in some cases also neuropathologically. Recently, a disease locus has been mapped to chromosome 4q21-22 in a large Mediterranean pedigree, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease- causing mutation has been identified in the gene encoding α-synuclein. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the α-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40{\%}. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.",
author = "T. Gasser and B. Muller-Myhsok and Wszolek, {Z. K.} and R. Oehlmann and Calne, {D. B.} and V. Bonifati and B. Bereznai and E. Fabrizio and P. Vieregge and Horstmann, {R. D.}",
year = "1998",
doi = "10.1038/ng0398-262",
language = "English",
volume = "18",
pages = "262--265",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - A susceptibility locus for Parkinson's disease maps to chromosome 2p13

AU - Gasser, T.

AU - Muller-Myhsok, B.

AU - Wszolek, Z. K.

AU - Oehlmann, R.

AU - Calne, D. B.

AU - Bonifati, V.

AU - Bereznai, B.

AU - Fabrizio, E.

AU - Vieregge, P.

AU - Horstmann, R. D.

PY - 1998

Y1 - 1998

N2 - Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease. Firstly, clinico- genetic, epidemiologic and twin studies revealed inheritable effects and questioned earlier studies which had denied such influences. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically and in some cases also neuropathologically. Recently, a disease locus has been mapped to chromosome 4q21-22 in a large Mediterranean pedigree, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease- causing mutation has been identified in the gene encoding α-synuclein. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the α-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40%. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.

AB - Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease. Firstly, clinico- genetic, epidemiologic and twin studies revealed inheritable effects and questioned earlier studies which had denied such influences. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically and in some cases also neuropathologically. Recently, a disease locus has been mapped to chromosome 4q21-22 in a large Mediterranean pedigree, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease- causing mutation has been identified in the gene encoding α-synuclein. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the α-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40%. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.

UR - http://www.scopus.com/inward/record.url?scp=0031951197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031951197&partnerID=8YFLogxK

U2 - 10.1038/ng0398-262

DO - 10.1038/ng0398-262

M3 - Article

C2 - 9500549

AN - SCOPUS:0031951197

VL - 18

SP - 262

EP - 265

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -