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

• 全文链接
• 请求原文
• 全文直达

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;  Chitsaz, Ahmad;  Shokraeian, Parasto;  Ehsanbakhsh, Hossein;  Rezaeidian, Jalal;  Rad, Reza Ebrahimi;  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;  Pour, Banafsheh Mohammad Hossein;  Moghaddam, Hamid Noorollahi;  Shandiz, Ehsan Esmaili;  Habibi, Arman;  Taherian-Esfahani, Zahra;  Darvish, Hossein;  Paisan-Ruiz, Coro; 

作者机构：

Dept Neurol;  Tabriz;  Babol Sar;  New York;  Noncommunicable Dis Res Ctr;  Imam Khomeini Hosp;  Toos Gen Hosp;  Fac Med;  Cellular & Mol Biol Res Ctr;  Univ Tehran Med Sci;  Dezful Univ Med Sci;  Iran;  Islamic Azad Univ;  Hazrat Rassol Hosp;  Sch Med;  Shiraz Univ Med Sci;  Jondi Shapoor Univ Med Sci;  Genet Res Ctr;  Babol Univ Med Sci;  Dept Med Genet;  Vali Abad Branch;  Neurol Dept;  Tabriz Univ Med Sci;  Tehran;  Isfahan Univ Med Sci;  Ahwaz;  Shahid Beheshti Univ Med Sci;  Shiraz;  Fasa;  NY 10029 USA;  Movement Disorders Clin;  Ganjavian Hosp;  Fasa Univ Med Sci;  Dezful;  Tonekabon;  Tehran Med Sci Branch;  Iran Univ Med Sci;  Icahn Sch Med Mt Sinai;  One Gustave L Levy Pl;  Univ Social Welf & Rehabil Sci;  Esfahan; 

关键词：

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

期刊名称：

Molecular Neurobiology

i s s n：

0893-7648

年卷期：

2018 年 55 卷 4 期

页   码：

3477-3489

页   码：

摘   要：

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.