Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism
Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism
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DOI：
10.1016/j.parkreldis.2018.10.012
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发表时间：
2019-04-01
影响因子：
4.1
通讯作者：
Leuzzi, Vincenzo
中科院分区：
文献类型：
--
作者：
Manti, Filippo;Nardecchia, Francesca;Leuzzi, Vincenzo
简介：网格蛋白在内吞、回收、运输以及突触前囊泡的产生中起着关键作用。我们报告了一个新的临床条件与CLTC基因，编码网格蛋白重polypeptide.Case报告这30岁的女子提出了一个发展障碍，在儿童期进展到轻度认知能力下降，在儿童后期和复发缓解性运动功能减退僵硬综合征严重失弛缓症，体重减轻，情绪障碍，在成年期。I-123-Ioflupane SPECT正常。血苯丙氨酸略有增加，PAH测序显示两种变体的复合杂合性，p。[Asp151Glu]：[Thr380Met]。结果在CLTC中检测到一个新的错义突变（c.2669C > T/p.Pro890Leu），该突变与四氢生物蝶呤和相关生物胺通路的改变无关。治疗与生物胺前体是无效的，而MAO-A司来吉兰的抑制剂导致持续的临床improvement.Conclusions：我们建议CLTC缺陷作为一个新的疾病的生物胺贩运，导致神经发育紊乱和运动障碍。CSF中神经递质的缺失可能是这种疾病的生物标志物，司来吉兰是一种可能的治疗选择。
Introduction: Clathrins play a key role in endocytosis, recycling, and trafficking as well as the generation of presynaptic vesicles. We report a new clinical condition associated with a de novo variant in the CLTC gene, which encodes the clathrin heavy polypeptide.Case report This 30-year-old woman presented with a developmental disorder during childhood that progressed to mild cognitive decline in late childhood and relapsing-remitting hypokinetic-rigid syndrome with severe achalasia, weight loss, and mood disorder in adulthood. I-123-Ioflupane SPECT was normal. Blood phenylalanine was slightly increased and PAH sequencing revealed compound heterozygosity for two variants, p.[Asp151Glu]: [Thr380Met]. CSF examination unexpectedly detected a remarkable reduction of homovanillic, 5-hydroxyindolacetic, and 5-methylthetrahydrofolic acids, which could not be ascribed to any alteration of tetrahydrobiopterin and related biogenic amine pathways.Methods: Trio-based exome sequencing was performed.Result A de novo missense variant (c.2669C > T/p.Pro890Leu) was detected in CLTC. Treatment with biogenic amine precursors was ineffective, while the inhibitor of MAO-A selegiline resulted in persistent clinical improvement.Conclusions: We suggest CLTC defect as a new disorder of biogenic amine trafficking, resulting in neurodevelopmental derangement and movement disorder. Neurotransmitter depletion in CSF may be a biomarker of this disease, and selegiline a possible treatment option.