Sahin Yavuz, Güngör Olcay, Gormez Zeliha, Demirci Huseyin, Ergüner Bekir, Güngör Gülay, Dilber Cengiz
Department of Medical Genetics, Necip Fazıl City Hospital, Kahramanmaras, 46050, Turkey.
Department of Child Neurology, Necip Fazıl City Hospital, Kahramanmaras, Turkey.
Acta Neurol Belg. 2017 Mar;117(1):159-167. doi: 10.1007/s13760-016-0721-3. Epub 2016 Nov 14.
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.
神经元蜡样脂褐质沉积症（NCL）是儿童期最常见的神经退行性疾病之一，其特征为常染色体隐性遗传、癫痫发作、进行性精神运动发育迟缓、视力损害和过早死亡。根据患者的来源国、该疾病的临床特征/病程以及分子遗传学背景，迄今为止已描述了14种不同的NCL亚型。CLN8突变最初在芬兰患者中被鉴定出来，这种病症被命名为北欧癫痫（NE）；然而，随后在芬兰以外地区发现了CLN8基因的严重表型，并将其命名为“变异型晚发性婴儿型”NCL。在本研究中，纳入了来自一个土耳其大家族的5名患者及其6名健康亲属。该研究涉及详细的临床、放射学和分子遗传学评估。全外显子组测序和纯合性定位揭示了一个新的纯合CLN8突变，即c.677T>C（p.Leu226Pro）。我们确定了土耳其由CLN8新突变引起的NE病例。全外显子组测序在病程不典型的罕见病例中可能是一种重要的诊断方法。
