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Exome sequencing identifies a novel homozygous CLN8 mutation in a Turkish family with Northern epilepsy

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Abstract

Neuronal ceroid lipofuscinosis (NCL), one of the most common neurodegenerative childhood-onset disorders, is characterized by autosomal-recessive inheritance, epileptic seizures, progressive psychomotor deterioration, visual impairment, and premature death. Based on the country of origin of the patients, the clinical features/courses, and the molecular genetics background of the disorder, 14 distinct NCL subtypes have been described to date. CLN8 mutation was first identified in Finnish patients, and the condition was named Northern Epilepsy (NE); however, the severe phenotype of the CLN8 gene was subsequently found outside Finland and named ‘variant late-infantile’ NCL. In this study, five patients and their six healthy relatives from a large Turkish consanguineous family were enrolled. The study involved detailed clinical, radiological and molecular genetic evaluations. Whole-exome sequencing and homozygosity mapping revealed a novel homozygous CLN8 mutation, c.677T>C (p.Leu226Pro). We defined NE cases in Turkey, caused by a novel mutation in CLN8. WES can be an important diagnostic method in rare cases with atypical courses.

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Acknowledgements

We would like to thank the family for their participation in this study. We appreciate AGBRG (IGBAM, Bilgem, TUBITAK) for sharing with us their massively parallel whole-exome sequencing results of 1182 private individuals.

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Authors and Affiliations

  1. Department of Medical Genetics, Necip Fazıl City Hospital, Kahramanmaras, 46050, Turkey

    Yavuz Sahin

  2. Department of Child Neurology, Necip Fazıl City Hospital, Kahramanmaras, Turkey

    Olcay Güngör

  3. Advanced Genomics and Bioinformatics Research Center (IGBAM), The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey

    Zeliha Gormez, Huseyin Demirci & Bekir Ergüner

  4. Department of Radiology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Gülay Güngör

  5. Department of Pediatric Neurology, Marash Life Hospital, Kahramanmaras, Turkey

    Cengiz Dilber

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  1. Yavuz Sahin
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  2. Olcay Güngör
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  3. Zeliha Gormez
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Correspondence to Yavuz Sahin.

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The authors declare that they acted in accordance with ethical standards laid down in the 1964 Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Sahin, Y., Güngör, O., Gormez, Z. et al. Exome sequencing identifies a novel homozygous CLN8 mutation in a Turkish family with Northern epilepsy. Acta Neurol Belg 117, 159–167 (2017). https://doi.org/10.1007/s13760-016-0721-3

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  • DOI: https://doi.org/10.1007/s13760-016-0721-3

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