Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease.
Parkinson's disease (PD; OMIM #168600) is the second most common neurodegenerative disorder in the Western world and presents as a progressive movement disorder. The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions. Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process. PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD. We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain. Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.
Paisán-Ruíz
Coro
C
Unitat de Genètica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València-CSIC, E46010 València, Spain.
Jain
Shushant
S
Evans
E Whitney
EW
Gilks
William P
WP
Simón
Javier
J
van der Brug
Marcel
M
López de Munain
Adolfo
A
Aparicio
Silvia
S
Gil
Angel Martínez
AM
Khan
Naheed
N
Johnson
Janel
J
Martinez
Javier Ruiz
JR
Nicholl
David
D
Martí Carrera
Itxaso
I
Pena
Amets Saénz
AS
de Silva
Rohan
R
Lees
Andrew
A
Martí-Massó
José Félix
JF
Pérez-Tur
Jordi
J
Wood
Nick W
NW
Singleton
Andrew B
AB
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005260:Female; D006239:Haplotypes; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D009419:Nerve Tissue Proteins; D011494:Protein Kinases; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases