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The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice
Author(s) -
Vural Atay,
Şimşir Gülşah,
Tekgül Şeyma,
Koçoğlu Cemile,
Akçimen Fulya,
Kartal Ece,
Şen Nesli E.,
Lahut Suna,
Ömür Özgür,
Saner Nazan,
Gül Tuğçe,
Bayraktar Elif,
Palvadeau Robin,
Tunca Ceren,
Pirkevi Çetinkaya Caroline,
Gündoğdu Eken Aslı,
Şahbaz Irmak,
Kovancılar Koç Müge,
Öztop Çakmak Özgür,
Hanağası Haşmet,
Bilgiç Başar,
Eraksoy Mefkure,
Gündüz Ayşegül,
Apaydın Hülya,
Kızıltan Güneş,
Özekmekçi Sibel,
Siva Aksel,
Altıntaş Ayşe,
Kaya Güleç Zeynep E.,
Parman Yeşim,
Oflazer Piraye,
Deymeer Feza,
Durmuş Hacer,
Şahin Erdi,
Çakar Arman,
Tüfekçioğlu Zeynep,
Tektürk Pınar,
Çorbalı M. Osman,
Tireli Hülya,
Akdal Gülden,
Yiş Uluç,
Hız Semra,
Şengün İhsan,
Bora Elçin,
Serdaroğlu Gül,
Erer Özbek Sevda,
Ağan Kadriye,
İnce Günal Dilek,
Us Önder,
Kurt Semiha G.,
Aksoy Dürdane,
Bora Tokçaer Ayşe,
Elmas Muhsin,
Gültekin Murat,
Kumandaş Sefer,
Acer Hamit,
Kaya Özçora Gül D.,
Yayla Vildan,
Soysal Aysun,
Genç Gençer,
Güllüoğlu Halil,
Kotan Dilcan,
Özözen Ayas Zeynep,
Şahin Hüseyin A.,
Tan Ersin,
Topçu Meral,
Topçuoğlu Esen Saka,
Akbostancı Cenk,
Koç Filiz,
Ertan Sibel,
Elibol Bülent,
Başak A. Nazlı
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28518
Subject(s) - proband , genetics , spinocerebellar ataxia , ataxia , exome sequencing , frataxin , sanger sequencing , medicine , genetic heterogeneity , population , genetic epidemiology , biology , phenotype , mutation , gene , psychiatry , iron binding proteins , environmental health
Background The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. Objective To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. Methods Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin ( FXN ) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole‐exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. Results Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix–Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole‐exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty‐eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. Conclusion With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society