Hasmet A Hanagasi1, Anamika Giri2, Ece Kartal3, Gamze Guven4, Başar Bilgiç5, Ann-Kathrin Hauser2, Murat Emre5, Peter Heutink2, Nazlı Basak3, Thomas Gasser2, Javier Simón-Sánchez2, Ebba Lohmann6. 1. Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey. Electronic address: hasmet@yahoo.com. 2. Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. 3. Department Molecular Biology and Genetics, Neurodegeneration Research Laboratory, Bogazici University, 34342, Istanbul, Turkey. 4. Institute for Experimental Medicine, Genetics Department, Istanbul University, Istanbul, Turkey. 5. Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey. 6. Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey; Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
Abstract
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.
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.
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