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

作者：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; Zarneh Amir Ehtesham Shafiei; Mohammadihosseinabad Saeed; Khorrami Mehdi; Najmi Safa

来源：Molecular Neurobiology, 2018, 55(4): 3477-3489.

DOI：10.1007/s12035-017-0535-1

• Early-onset
• Parkinson's disease
• Pathogenic mutations
• Genotype-phenotype correlations

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.

• 出版日期2018-4