Prenatal-onset of congenital neuronal ceroid lipofuscinosis with a novel CTSD mutation
Prenatal-onset of congenital neuronal ceroid lipofuscinosis with a novel CTSD mutation
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DOI：
10.1002/bdr2.1950
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发表时间：
2021-09-07
影响因子：
2.1
通讯作者：
Attie-Bitach, Tania
中科院分区：
文献类型：
--
作者：
Chartier, Suzanne;Boutaud, Lucile;Attie-Bitach, Tania
神经蜡样脂褐质病（NCLs）是一种临床和遗传异质性的遗传性神经退行性疾病，具有共同的神经病理特征。虽然它们是儿童神经退行性疾病的首要原因，但它们的先天性形式很少有文献记载。它们通常是由CTSD基因（CLN10疾病）突变引起的。受影响的新生儿通常出现严重的小头畸形、癫痫发作和呼吸衰竭，导致在出生后几天或几周内死亡。我们报告了两个兄弟姐妹，其中外显子组测序鉴定出一种新的纯合子CTSD变体。第一个兄弟姐妹在出生时表现为癫痫发作，产后快速进行性小头畸形和与视网膜功能障碍有关的视力缺陷。进行性神经退化导致24个月大时死亡。该患者培养成纤维细胞中组织蛋白酶D活性降低。第二个兄弟姐妹是妊娠36周的胎儿，在因大脑异常（根据法国法律）而终止妊娠后出生，这表明该疾病复发。胎儿死后检查显示神经病理特征符合NCL。结论与CTSD突变相关的先天性NCL是一种神经元储存障碍，在发育中的脑弥漫性神经变性和白质萎缩导致进行性和快速致命的小头畸形。
Background Neuronal ceroid lipofuscinoses (NCLs) form a clinically and genetically heterogeneous group of inherited neurodegenerative disorders that share common neuropathological features. Although they are the first cause of neurodegenerative disorders in children, their congenital forms are rarely documented. They are classically due to mutations in the CTSD gene (the CLN10 disease). Affected newborns usually present severe microcephaly, seizures and respiratory failure leading to death within the first postnatal days or weeks. Cases We report on two siblings, in which exome sequencing identified a novel homozygous CTSD variant. The first sib presented at birth with seizures, rapidly progressive postnatal microcephaly and visual deficiency related to retinal dysfunction. Progressive neurological deterioration leads to death at the age of 24 months. Cathepsin D activity was reduced in the cultured fibroblasts of this patient. The second sib, a fetus of 36 weeks of gestation, was delivered after pregnancy termination for brain abnormalities (in accordance with French Legislation) suggesting a recurrence of the disease. Fetal postmortem examination disclosed neuropathological features consistent with NCL. Conclusions Congenital NCL related to CTSD mutations is a neuronal storage disorder that produces in the developing brain diffuse neurodegeneration and white matter atrophy resulting in a progressive and rapidly lethal microcephaly.