Unit of Human Biology and Genetics, The Triangle Regional Research and Development Center, Kafr Qara 30075, Israel.
Beit-Berl Academic College, Beit-Berl 4490500, Israel.
Genes (Basel). 2022 Aug 5;13(8):1393. doi: 10.3390/genes13081393.
The CLN8 disease type refers to one of the neuronal ceroid lipofuscinoses (NCLs) which are the most common group of neurodegenerative diseases in childhood. The clinical phenotypes of this disease are progressive neurological deterioration that could lead to seizures, dementia, ataxia, visual failure, and various forms of abnormal movement. In the current study, we describe two patients who presented with atypical phenotypic manifestation and protracted clinical course of CLN8 carrying a novel compound heterozygous variant at the gene. Our patients developed a mild phenotype of CLN8 disease: as they presented mild epilepsy, cognitive decline, mild learning disability, attention-deficit/hyperactivity disorder (ADHD), they developed a markedly protracted course of motor decline. Bioinformatic analyses of the compound heterozygous gene variants were carried out. Most of the variants seem likely to act by compromising the structural integrity of regions within the protein. This in turn is expected to reduce the overall stability of the protein and render the protein less active to various degrees. The cases in our study confirmed and expanded the effect of compound heterozygous variants in CLN8 disease.
CLN8 疾病类型属于神经元蜡样脂褐质沉积症（NCL）中的一种，NCL 是儿童期最常见的神经退行性疾病之一。这种疾病的临床表型为进行性神经功能恶化，可能导致癫痫、痴呆、共济失调、视力丧失和各种形式的异常运动。在本研究中，我们描述了两名表现出非典型表型和 CLN8 延长临床病程的患者，他们携带 基因的新型复合杂合变异。我们的患者表现出轻度 CLN8 疾病表型：他们表现出轻度癫痫、认知能力下降、轻度学习障碍、注意力缺陷/多动障碍（ADHD），运动能力下降的病程明显延长。对复合杂合 基因变异进行了生物信息学分析。大多数变异似乎很可能通过破坏蛋白内区域的结构完整性起作用。这反过来又预计会降低蛋白质的整体稳定性，并使其在不同程度上降低活性。本研究中的病例证实并扩展了 CLN8 疾病中复合杂合变异的影响。
