The distinct genetic pattern of ALS in Turkey and novel mutations

NEUROBIOLOGY OF AGING

卷:36

Article

Ozoguz, Aslihan¹  Uyan, Ozgun¹  Birdal, Gunes¹  Iskender, Ceren¹  Kartal, Ece¹  Lahut, Suna¹  Omur, Ozgur¹  Agim, Zeynep Sena¹  Eken, Asli Gundogdu¹  Sen, Nesli Ece¹  Saygi, Ceren¹  Sapp, Peter C.³  Keagle, Pamela^2,3  Parman, Yesim⁴  Tan, Ersin⁵  Koc, Filiz⁶  Deymeer, Feza⁴  Oflazer, Piraye⁴  Hanagasi, Hasmet⁴  Bilgic, Basar⁴  Durmus, Hacer⁴  Ertas, Mustafa⁷  Kotan, Dilcan⁸  Akalin, Mehmet Ali⁹  Gulluoglu, Halil¹⁰  Zarifoglu, Mehmet¹¹  Aysal, Fikret¹²  Dosolu, Nilgun¹³  Bilguvar, Kaya^13,14  Gunel, Murat¹⁴  Keskin, Ozlem¹⁵  Akgun, Tahsin¹⁶  Ozcelik, Hilmi¹⁷  Landers, John E.³  Brown, Robert H.³  Basak, A. Nazli¹ 

[1] Bogazici Univ, Neurodegenerat Res Lab NDAL, Suna & Inan Kirac Fdn, Mol Biol & Genet Dept, TR-34342 Istanbul, Turkey

[2] Bogazici Univ, Dept Comp Engn, TR-34342 Istanbul, Turkey

[3] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA

[4] Istanbul Univ, Istanbul Med Sch, Dept Neurol, Istanbul, Turkey

[5] Hacettepe Univ, Sch Med, Dept Neurol, Ankara, Turkey

[6] Cukurova Univ, Sch Med, Dept Neurol, Adana, Turkey

[7] Liv Hosp, Dept Neurol, Istanbul, Turkey

[8] Sakarya Univ, Fac Med, Dept Neurol, Sakarya, Turkey

[9] Istanbul Univ, Cerrahpasa Med Sch, Dept Neurol, Istanbul, Turkey

[10] Med Pk Izmir Hosp, Dept Neurol, Izmir, Turkey

[11] Uludag Univ, Sch Med, Dept Neurol, Bursa, Turkey

[12] Bakirkoy Res & Training Hosp Neurol & Psychiat Di, Istanbul, Turkey

[13] Haydarpasa Numune Educ & Res Hosp, Istanbul, Turkey

[14] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA

[15] Koc Univ, Chem & Biol Engn Dept, Istanbul, Turkey

[16] Amer Hosp, Dept Anesthesiol & Reanimat, Istanbul, Turkey

[17] Univ Toronto, Samuel Lunenfeld Res Inst, Dept Pathol & Lab Med, Toronto, ON, Canada

关键词: ALS;    Turkey;    SOD1;    C9orf72;    TDP-43;    FUS;   

DOI  :  10.1016/j.neurobiolaging.2014.12.032

来源: Elsevier

【 摘 要 】

The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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