title: Exome sequencing identifies a novel homozygous CLN8 mutation in a Turkish family with Northern epilepsy.
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.
authors.affiliation: Department of Medical Genetics, Necip Fazıl City Hospital, Kahramanmaras, 46050, Turkey. mdysahin@gmail.com.
authors.forename: Yavuz
authors.identifier: http://orcid.org/0000-0002-7831-067X
authors.initials: Y
authors.lastname: Sahin
authors.affiliation: Department of Child Neurology, Necip Fazıl City Hospital, Kahramanmaras, Turkey.
authors.forename: Olcay
authors.initials: O
authors.lastname: Güngör
authors.affiliation: Advanced Genomics and Bioinformatics Research Center (IGBAM), The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Gormez
authors.affiliation: Advanced Genomics and Bioinformatics Research Center (IGBAM), The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Demirci
authors.affiliation: Advanced Genomics and Bioinformatics Research Center (IGBAM), The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
authors.forename: Bekir
authors.initials: B
authors.lastname: Ergüner
authors.affiliation: Department of Radiology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Gülay
authors.initials: G
authors.lastname: Güngör
authors.affiliation: Department of Pediatric Neurology, Marash Life Hospital, Kahramanmaras, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Dilber
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010375:Pedigree; D014421:Turkey; D055815:Young Adult
chemical_list: C121767:CLN8 protein, human; D008565:Membrane Proteins
keywords: CLN8; NCL; Neuronal ceroid lipofuscinosis; Northern epilepsy