Miller Jake N, Pearce David A
Sanford Children's Health Research Center, Sanford Research, Sioux Falls, SD, USA.
J Child Neurol. 2013 Sep;28(9):1106-11. doi: 10.1177/0883073813494267. Epub 2013 Jul 14.
The neuronal ceroid lipofuscinoses are the most common autosomal recessive neurodegenerative disorders in children, with a worldwide incidence of 1 in 100,000 live births. Multiple clinical variants are caused by more than 400 mutations in at least 14 different genes. These progressive genetic disorders primarily manifest in the central nervous system because of an extensive loss of neurons, specifically in the cerebral and cerebellar cortices. Patients with mutations in CLN1, which encodes palmitoyl-protein thioesterase 1 (PPT1), primarily manifest with infantile neuronal ceroid lipofuscinosis (Haltia-Santavuori disease). Affected children usually present between 1 and 2 years of age and typically die by 8 to 13 years of age. We describe a patient with infantile neuronal ceroid lipofuscinosis with a novel c.776_777insA mutation in CLN1. This insertion induces a frameshift and a premature stop codon late within the CLN1 messenger RNA (mRNA) transcript which is likely recognized by nonsense-mediated translation repression, decreasing PPT1 abundance.
神经元蜡样脂褐质沉积症是儿童中最常见的常染色体隐性神经退行性疾病，全球活产发病率为十万分之一。多种临床变异由至少14个不同基因中的400多种突变引起。这些进行性遗传疾病主要在中枢神经系统表现出来，原因是神经元大量丧失，特别是在大脑和小脑皮质。编码棕榈酰蛋白硫酯酶1（PPT1）的CLN1发生突变的患者主要表现为婴儿型神经元蜡样脂褐质沉积症（哈尔蒂亚 - 桑塔沃里病）。受影响的儿童通常在1至2岁之间发病，通常在8至13岁时死亡。我们描述了一名患有婴儿型神经元蜡样脂褐质沉积症的患者，其CLN1基因存在一种新的c.776_777insA突变。这种插入导致移码，并在CLN1信使核糖核酸（mRNA）转录本中较晚出现提前终止密码子，这可能被无义介导的翻译抑制所识别，从而降低PPT1的丰度。
