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

2017; Springer Science+Business Media; Volume: 55; Issue: 4 Linguagem: Inglês

10.1007/s12035-017-0535-1

1559-1182

Shaghayegh Taghavi, Rita Chaouni, Abbas Tafakhori, Luís Azcona, Saghar Ghasemi Firouzabadi, Mir Davood Omrani, Javad Jamshidi, Babak Emamalizadeh, Gholam Ali Shahidi, Mona Ahmadi, Seyed Amir Hassan Habibi, Azadeh Ahmadifard, Atena Fazeli, Marzieh Motallebi, Peyman Petramfar, Saeed Askarpour, Shiva Askarpour, Hossein Ali Shahmohammadibeni, Neda Shahmohammadibeni, Hajar Eftekhari, Amir Ehtesham Shafiei Zarneh, Saeed Mohammadihosseinabad, Mehdi Khorrami, Safa Najmi, Ahmad Chitsaz, Parasto Shokraeian, Hossein Ehsanbakhsh, Jalal Rezaeidian, Reza Ebrahimi Rad, Faranak Madadi, Monavvar Andarva, Elham Alehabib, Minoo Atakhorrami, Seyed Erfan Mortazavi, Zahra Azimzadeh, Mahdis Bayat, Amir Mohammad Besharati, Mohammad Ali Harati-Ghavi, Samareh Omidvari, Zahra Dehghani-Tafti, Faraz Mohammadi, Banafsheh Mohammad Hossein Pour, Hamid Noorollahi Moghaddam, Ehsan Esmaili Shandiz, Arman Habibi, Zahra Taherian‐Esfahani, Hossein Darvish, Coro Paisán‐Ruiz,

Nuclear Receptors and Signaling

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.