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Abstract：
Variants in the ERCC4 gene have been described to be associated with the following autosomal recessive diseases: xeroderma pigmentosum group F (XPF), xeroderma pigmentosum type F/Cockayne syndrome (XPF/CS), Fanconi anemia complementation group Q (FANCQ), and XFE progeroid syndrome (XFEPS). In this paper, we present a case of a 53-year-old Caucasian female patient with rare variants in the ERCC4 gene. When she was 42 years old, falls and loss of balance occurred. At the age of 48, involuntary, uncoordinated movements of the upper limbs and head, tongue stereotypes (licking and extending movements), speech problems (dysarthria), memory deterioration, and hearing loss occurred. Since childhood, she has shown hypersensitivity to UV radiation. The neurological examination revealed chorea syndrome, cerebellar ataxia, dysarthria, and bilateral hearing loss. She has numerous pigmented lesions on the skin. Brain MRI demonstrated massive cortico-subcortical atrophy. The neuropsychological examination revealed dysfunctions in the executive domain in terms of attention, working memory, organizing, and planning activities. The genetic diagnostics was performed which excluded spinocerebellar ataxia types 1, 2, 3, 6, and 17, Huntington\'s disease, and FMR1 premutation. In the genetic analysis of next-generation sequencing (NGS), two variants: c.2395C > T and c.1349G > A in the ERCC4 gene were identified in a heterozygote configuration. So far, a few cases of ERCC4 gene variants, which are associated with nucleotide excision repair pathways, have been described in connection with symptoms of cerebellar ataxia. In patients with ERCC4 biallelic variants, the adult neurological phenotype can sometimes be the first symptom and reason for access to genetic testing. The aforementioned case highlights the occurrence of rare genetic causes of progressive neurodegenerative diseases in adults, especially with the spectrum of autosomal recessive nucleotide excision repair pathway disorders (NERDs).
摘要：
已经描述了ERCC4基因的变异与以下常染色体隐性遗传疾病有关：色素性干皮病F组（XPF），色素性干皮病F/Cockayne综合征(XPF/CS),范可尼贫血补充组Q（FANCQ），和XFE早孕综合征（XFEPS）。在本文中,我们报道了1例ERCC4基因罕见变异的53岁白种人女性患者.当她42岁的时候，跌倒和失去平衡。48岁时，非自愿，上肢和头部的不协调运动，舌头定型(舔和延伸动作)，言语问题（构音障碍），记忆力衰退，发生了听力损失。从小,她对紫外线辐射过敏.神经系统检查显示舞蹈症综合征,小脑共济失调,构音障碍,和双侧听力损失。她皮肤上有许多色素性病变。脑MRI显示大量皮质-皮质下萎缩。神经心理学检查揭示了执行领域在注意力方面的功能障碍，工作记忆,组织,和规划活动。进行基因诊断，排除脊髓小脑性共济失调类型1，2，3，6和17，亨廷顿病，和FMR1预突变。在下一代测序（NGS）的遗传分析中，ERCC4基因中的两个变体:c.2395C>T和c.1349G>A以杂合子构型鉴定。到目前为止,几例ERCC4基因变异，与核苷酸切除修复途径有关，已被描述与小脑共济失调的症状有关。在ERCC4双等位基因变异的患者中，成人神经表型有时可能是获得基因检测的第一个症状和原因。上述病例强调了成人进行性神经退行性疾病的罕见遗传原因的发生，特别是常染色体隐性遗传核苷酸切除修复途径障碍（NERD）。
