A novel homozygous DJ1 mutation causes parkinsonism and ALS in a Turkish family

Autor: Ebba Lohmann, Peter Heutink, Murat Emre, Thomas Gasser, Hasmet Hanagasi, Başar Bilgiç, Ece Kartal, Javier Simón-Sánchez, Nazli Basak, Gamze Guven, Anamika Giri, Ann-Kathrin Hauser
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
Pediatrics
medicine.medical_specialty
Parkinson's disease
Turkey
Genetic counseling
DNA Mutational Analysis
Protein Deglycase DJ-1
genetics [Protein Deglycase DJ-1]
genetics [Mutation]
Consanguinity
Severity of Illness Index
03 medical and health sciences
0302 clinical medicine
genetics [Parkinson Disease]
Humans
Medicine
ddc:610
Sibling
Amyotrophic lateral sclerosis
Index case
Family Health
Genetics
business.industry
Parkinsonism
Amyotrophic Lateral Sclerosis
Computational Biology
Parkinson Disease
medicine.disease
genetics [Amyotrophic Lateral Sclerosis]
030104 developmental biology
Neurology
PARK7 protein
human
Mutation
Mutation (genetic algorithm)
complications [Amyotrophic Lateral Sclerosis]
Female
Neurology (clinical)
complications [Parkinson Disease]
Geriatrics and Gerontology
Mental Status Schedule
business
030217 neurology & neurosurgery
Zdroj: Parkinsonism & related disorders 29, 117-120 (2016). doi:10.1016/j.parkreldis.2016.03.001
ISSN: 1353-8020
DOI: 10.1016/j.parkreldis.2016.03.001
Popis: Objective DJ1 mutations (PARK7) are among the monogenic causes of early-onset autosomal recessive parkinsonism. Here, we report clinical and genetic findings in a family with Turkish origin carrying a new DJ1 mutation and presenting with early-onset levodopa responsive parkinsonism and signs of amyotrophic lateral sclerosis (ALS). Methods The family consisted of 12 members including 10 offsprings of whom three were affected. All family members underwent detailed clinical examination. DNA samples from the index case, his unaffected sister, and his parents were subjected to whole genome sequencing analysis. Results The index case 38-year-old man developed left hand tremor at the age of 24 years. He had progressive asymmetrical parkinsonism, depression and developed signs of ALS within 4 years. His two affected sisters had young-onset asymmetrical tremor-dominant parkinsonism with signs of ALS. A new homozygous p.Q45X mutation in exon 3 in DJ1 was found in all three patients. Their unaffected parents and one clinically healthy sibling were found to be heterozygous for this mutation. Conclusions This is the second report of DJ1 mutations associated with parkinsonism and ALS. This is relevant for genetic counseling as well as for understanding the pathogenesis of the broad spectrum of parkinsonism-ALS disease complex.
Databáze: OpenAIRE
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