A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations

In this study, the role of known Parkinson’s disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to ident...

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Published in:	Molecular neurobiology Vol. 55; no. 4; pp. 3477 - 3489
Main Authors:	Taghavi, Shaghayegh, Chaouni, Rita, Tafakhori, Abbas, Azcona, Luis J., Firouzabadi, Saghar Ghasemi, Omrani, Mir Davood, Jamshidi, Javad, Emamalizadeh, Babak, Shahidi, Gholam Ali, Ahmadi, Mona, Habibi, Seyed Amir Hassan, Ahmadifard, Azadeh, Fazeli, Atena, Motallebi, Marzieh, Petramfar, Peyman, Askarpour, Saeed, Askarpour, Shiva, Shahmohammadibeni, Hossein Ali, Shahmohammadibeni, Neda, Eftekhari, Hajar, Shafiei Zarneh, Amir Ehtesham, Mohammadihosseinabad, Saeed, Khorrami, Mehdi, Najmi, Safa, Chitsaz, Ahmad, Shokraeian, Parasto, Ehsanbakhsh, Hossein, Rezaeidian, Jalal, Ebrahimi Rad, Reza, Madadi, Faranak, Andarva, Monavvar, Alehabib, Elham, Atakhorrami, Minoo, Mortazavi, Seyed Erfan, Azimzadeh, Zahra, Bayat, Mahdis, Besharati, Amir Mohammad, Harati-Ghavi, Mohammad Ali, Omidvari, Samareh, Dehghani-Tafti, Zahra, Mohammadi, Faraz, Mohammad Hossein Pour, Banafsheh, Noorollahi Moghaddam, Hamid, Esmaili Shandiz, Ehsan, Habibi, Arman, Taherian-Esfahani, Zahra, Darvish, Hossein, Paisán-Ruiz, Coro
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-04-2018 Springer Nature B.V
Subjects:	Adult Amino Acid Sequence Basal ganglia Base Sequence Biomedical and Life Sciences Biomedicine Brain diseases Cell Biology Central nervous system diseases Consanguinity Differential diagnosis Exons - genetics Family Female Genes Genomes Heredity Humans Male Membrane Proteins - genetics Middle Aged Movement disorders Mutation Mutation - genetics Neurobiology Neurodegenerative diseases Neurological disorders Neurology Neurosciences PARK7 protein Parkin protein Parkinson's disease Parkinsonian Disorders - genetics Phosphoric Monoester Hydrolases - genetics Protein Kinases - genetics PTEN-induced putative kinase Ubiquitin-Protein Ligases - genetics Young Adult Genotype-phenotype correlations Pathogenic mutations Early-onset Parkinson’s disease
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Summary:	In this study, the role of known Parkinson’s disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin , PINK1 , DJ-1 , SYNJ1 , and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0893-7648 1559-1182
DOI:	10.1007/s12035-017-0535-1