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

• Published in: Parkinsonism & related disorders Vol. 29; pp. 117 - 120
• Main Authors: Hanagasi, Hasmet A, Giri, Anamika, Kartal, Ece, Guven, Gamze, Bilgiç, Başar, Hauser, Ann-Kathrin, Emre, Murat, Heutink, Peter, Basak, Nazlı, Gasser, Thomas, Simón-Sánchez, Javier, Lohmann, Ebba
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2016
• Subjects: Adult; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - complications; Amyotrophic Lateral Sclerosis - genetics; Computational Biology; Consanguinity; DJ1; DNA Mutational Analysis; Family Health; Female; Humans; Male; Mental Status Schedule; Mutation - genetics; Neurology; PARK7; Parkinson Disease - complications; Parkinson Disease - genetics; Parkinson's disease; Protein Deglycase DJ-1 - genetics; Severity of Illness Index; Turkey; Amyotrophic lateral sclerosis; DJ1; Parkinson's disease; PARK7
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2016.03.001

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.