Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1.
BACKGROUND
Mutations in the PTEN-induced putative kinase 1 (PINK1) gene at 1p36 have been involved in autosomal recessive early-onset parkinsonism.


OBJECTIVE
To describe the clinical and genetic features of the largest kindred reported to date with early-onset parkinsonism associated with the PINK1 gene.


METHODS
Clinical and genetic study.


METHODS
Collaborative study. Patients Eight patients from Sudan with particularly early onset (ages 9-17 years) and phenotypes varying from dopa-responsive dystonia-like to typical early-onset parkinsonism.


METHODS
The PINK1 genotype and Parkinson disease status of all available family members.


RESULTS
The disease was caused by a novel mutation, p.A217D, located in the highly conserved adenosine triphosphate orientation site of the PINK1 kinase domain.


CONCLUSIONS
This study extends the phenotypic and molecular spectrum of the PINK1 gene and the geographic origin of patients with PINK1 gene mutations.
Leutenegger
Anne-Louise
AL
Institut National de la Santé et de la Recherche Médicale U679, Assistance Publique, Hôpitaux de Paris, Faculté de Médecine, Université Paris 6-Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, 47 Blvd. de l'Hôpital, 75651 Paris CEDEX 13, France.
Salih
Mustafa A M
MA
Ibáñez
Pablo
P
Mukhtar
Maowia M
MM
Lesage
Suzanne
S
Arabi
Ali
A
Lohmann
Ebba
E
Dürr
Alexandra
A
Ahmed
Ammar E M
AE
Brice
Alexis
A
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D013397:Sudan; D000099202:PTEN-Induced Putative Kinase
D000255:Adenosine Triphosphate; D000409:Alanine; D001224:Aspartic Acid; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase