Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr;36(4):1764.e9-1764.e18.
doi: 10.1016/j.neurobiolaging.2014.12.032. Epub 2015 Jan 10.

The distinct genetic pattern of ALS in Turkey and novel mutations

Aslıhan Özoğuz  1 , Özgün Uyan  1 , Güneş Birdal  1 , Ceren Iskender  1 , Ece Kartal  1 , Suna Lahut  1 , Özgür Ömür  1 , Zeynep Sena Agim  1 , Aslı Gündoğdu Eken  1 , Nesli Ece Sen  1 , Pınar Kavak  2 , Ceren Saygı  1 , Peter C Sapp  3 , Pamela Keagle  3 , Yeşim Parman  4 , Ersin Tan  5 , Filiz Koç  6 , Feza Deymeer  4 , Piraye Oflazer  4 , Haşmet Hanağası  4 , Hakan Gürvit  4 , Başar Bilgiç  4 , Hacer Durmuş  4 , Mustafa Ertaş  7 , Dilcan Kotan  8 , Mehmet Ali Akalın  9 , Halil Güllüoğlu  10 , Mehmet Zarifoğlu  11 , Fikret Aysal  12 , Nilgün Döşoğlu  13 , Kaya Bilguvar  14 , Murat Günel  14 , Özlem Keskin  15 , Tahsin Akgün  16 , Hilmi Özçelik  17 , John E Landers  3 , Robert H Brown  3 , A Nazlı Başak  18
Affiliations

The distinct genetic pattern of ALS in Turkey and novel mutations

Aslıhan Özoğuz et al. Neurobiol Aging. 2015 Apr.

Abstract

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.

Keywords: ALS; C9orf72; FUS; SOD1; TDP-43; Turkey.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement

The authors declare no conflicts of interest. DNA samples were collected with the approval of the relevant institutional ethic boards, and informed written consent was obtained from each participant.

Figures

Fig. 1.
Fig. 1.
Distribution of amyotrophic lateral sclerosis mutations in Turkey. Cities of origin are shown, the brackets indicate the number of families, and the asterisk specifies novel mutations.
Fig. 2.
Fig. 2.
Five Turkish pedigrees with different ALS mutations.
Fig. 3.
Fig. 3.
Turkish pedigrees with UBQLN2 mutations
See this image and copyright information in PMC

References

    1. Al-Chalabi A, Jones A, Troakes C, King A, Al-Sarraj S, van den Berg LH, 2012. The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuro-pathol. 124, 339–352. - PubMed
    1. Andersen PM, Al-Chalabi A, 2011. Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat. Rev. Neurol 7, 603–615. - PubMed
    1. Andersen PM, Nilsson P, Ala-Hurula V, Keranen ML, Tarvainen I, Haltia T, Nilsson L, Binzer M, Forsgren L, Marklund SL, 1995. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet 10, 61–66. - PubMed
    1. Annesi G, Savettieri G, Pugliese P, D’Amelio M, Tarantino P, Ragonese P, La Bella V, Piccoli T, Civitelli D, Annesi F, Fierro B, Piccoli F, Arabia G, Caracciolo M, Ciro Candiano IC, Quattrone A, 2005. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann. Neurol 58, 803–80. - PubMed
    1. Battistini S, Giannini F, Greco G, Bibbo G, Ferrera L, Marini V, Causarano R, Casula M, Lando G, Patrosso MC, Caponnetto C, Origone P, Marocchi A, Del Corona A, Siciliano G, Carrera P, Mascia V, Giagheddu M, Carcassi C, Orru S, Garre C, Penco S, 2005. SOD1 mutations in amyotrophic lateral sclerosis. Results from a multicenter Italian study. J. Neurol 252, 782–788. - PubMed

Publication types

MeSH terms

Substances