Novel parkin mutations detected in patients with early-onset Parkinson's disease

A.M. Bertoli-Avella, J.L. Giroud-Benitez, A. Akyol, E. Barbosa, O. Schaap, H.C. van der Linde, E. Martignoni, L. Lopiano, P. Lamberti, E. Fincati, A. Antonini, F. Stocchi, P. Montagna, F. Squitieri, P. Marini, G. Abbruzzese, G. Fabbrini, R. Marconi, A. Dalla Libera, G. Trianni & 12 others M. Guidi, A. de Gaetano, G. Boff Maegawa, A. de Leo, V. Gallai, G. de Rosa, N. Vanacore, G. Meco, C.M. van Duijn, B.A. Oostra, P. Heutink, V. Bonifati

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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, IVS113C>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. © 2004 Movement Disorder Society.
Original languageEnglish
Pages (from-to)424-431
JournalMovement Disorders
Volume20
Issue number4
DOIs
Publication statusPublished - 2005

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Parkinson Disease
Mutation
Exons
Genetic Testing
Age of Onset
Disease Progression
Alleles
Genotype
Phenotype
Genes

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Bertoli-Avella, A. M., Giroud-Benitez, J. L., Akyol, A., Barbosa, E., Schaap, O., van der Linde, H. C., ... Bonifati, V. (2005). Novel parkin mutations detected in patients with early-onset Parkinson's disease. Movement Disorders, 20(4), 424-431. https://doi.org/10.1002/mds.20343
Bertoli-Avella, A.M. ; Giroud-Benitez, J.L. ; Akyol, A. ; Barbosa, E. ; Schaap, O. ; van der Linde, H.C. ; Martignoni, E. ; Lopiano, L. ; Lamberti, P. ; Fincati, E. ; Antonini, A. ; Stocchi, F. ; Montagna, P. ; Squitieri, F. ; Marini, P. ; Abbruzzese, G. ; Fabbrini, G. ; Marconi, R. ; Dalla Libera, A. ; Trianni, G. ; Guidi, M. ; de Gaetano, A. ; Boff Maegawa, G. ; de Leo, A. ; Gallai, V. ; de Rosa, G. ; Vanacore, N. ; Meco, G. ; van Duijn, C.M. ; Oostra, B.A. ; Heutink, P. ; Bonifati, V. / Novel parkin mutations detected in patients with early-onset Parkinson's disease. In: Movement Disorders. 2005 ; Vol. 20, No. 4. pp. 424-431.
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title = "Novel parkin mutations detected in patients with early-onset Parkinson's disease",
abstract = "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, IVS113C>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. {\circledC} 2004 Movement Disorder Society.",
author = "A.M. Bertoli-Avella and J.L. Giroud-Benitez and A. Akyol and E. Barbosa and O. Schaap and {van der Linde}, H.C. and E. Martignoni and L. Lopiano and P. Lamberti and E. Fincati and A. Antonini and F. Stocchi and P. Montagna and F. Squitieri and P. Marini and G. Abbruzzese and G. Fabbrini and R. Marconi and {Dalla Libera}, A. and G. Trianni and M. Guidi and {de Gaetano}, A. and {Boff Maegawa}, G. and {de Leo}, A. and V. Gallai and {de Rosa}, G. and N. Vanacore and G. Meco and {van Duijn}, C.M. and B.A. Oostra and P. Heutink and V. Bonifati",
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Bertoli-Avella, AM, Giroud-Benitez, JL, Akyol, A, Barbosa, E, Schaap, O, van der Linde, HC, Martignoni, E, Lopiano, L, Lamberti, P, Fincati, E, Antonini, A, Stocchi, F, Montagna, P, Squitieri, F, Marini, P, Abbruzzese, G, Fabbrini, G, Marconi, R, Dalla Libera, A, Trianni, G, Guidi, M, de Gaetano, A, Boff Maegawa, G, de Leo, A, Gallai, V, de Rosa, G, Vanacore, N, Meco, G, van Duijn, CM, Oostra, BA, Heutink, P & Bonifati, V 2005, 'Novel parkin mutations detected in patients with early-onset Parkinson's disease' Movement Disorders, vol. 20, no. 4, pp. 424-431. https://doi.org/10.1002/mds.20343

Novel parkin mutations detected in patients with early-onset Parkinson's disease. / Bertoli-Avella, A.M.; Giroud-Benitez, J.L.; Akyol, A.; Barbosa, E.; Schaap, O.; van der Linde, H.C.; Martignoni, E.; Lopiano, L.; Lamberti, P.; Fincati, E.; Antonini, A.; Stocchi, F.; Montagna, P.; Squitieri, F.; Marini, P.; Abbruzzese, G.; Fabbrini, G.; Marconi, R.; Dalla Libera, A.; Trianni, G.; Guidi, M.; de Gaetano, A.; Boff Maegawa, G.; de Leo, A.; Gallai, V.; de Rosa, G.; Vanacore, N.; Meco, G.; van Duijn, C.M.; Oostra, B.A.; Heutink, P.; Bonifati, V.

In: Movement Disorders, Vol. 20, No. 4, 2005, p. 424-431.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Novel parkin mutations detected in patients with early-onset Parkinson's disease

AU - Bertoli-Avella, A.M.

AU - Giroud-Benitez, J.L.

AU - Akyol, A.

AU - Barbosa, E.

AU - Schaap, O.

AU - van der Linde, H.C.

AU - Martignoni, E.

AU - Lopiano, L.

AU - Lamberti, P.

AU - Fincati, E.

AU - Antonini, A.

AU - Stocchi, F.

AU - Montagna, P.

AU - Squitieri, F.

AU - Marini, P.

AU - Abbruzzese, G.

AU - Fabbrini, G.

AU - Marconi, R.

AU - Dalla Libera, A.

AU - Trianni, G.

AU - Guidi, M.

AU - de Gaetano, A.

AU - Boff Maegawa, G.

AU - de Leo, A.

AU - Gallai, V.

AU - de Rosa, G.

AU - Vanacore, N.

AU - Meco, G.

AU - van Duijn, C.M.

AU - Oostra, B.A.

AU - Heutink, P.

AU - Bonifati, V.

PY - 2005

Y1 - 2005

N2 - 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, IVS113C>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. © 2004 Movement Disorder Society.

AB - 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, IVS113C>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. © 2004 Movement Disorder Society.

U2 - 10.1002/mds.20343

DO - 10.1002/mds.20343

M3 - Article

VL - 20

SP - 424

EP - 431

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 4

ER -

Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC et al. Novel parkin mutations detected in patients with early-onset Parkinson's disease. Movement Disorders. 2005;20(4):424-431. https://doi.org/10.1002/mds.20343