Universitätsklinikum Münster, Klinik für Kinder und Jugendmedizin, Münster, Germany.
Am J Med Genet A. 2021 Mar;185(3):930-936. doi: 10.1002/ajmg.a.62048. Epub 2020 Dec 27.
DNA damage repair is a pivotal mechanism in life. The nucleotide excision repair pathway protects the cells against DNA damage and involves XPD, an ATP dependent helicase that is part of the multisubunit protein complex TFIIH. XPD is encoded by the excision repair cross-complementation group 2 gene (ERCC2). Only three patients with cerebro-oculo-facio-skeletal syndrome (COFS), caused by mutations in ERCC2, have been published so far. This report describes a boy with the homozygous amino acid change p.Gly47Arg in XPD. He presented with profound microcephaly, psychomotor retardation, failure to thrive, cutaneous photosensitivity, a bilateral hearing deficit and optic atrophy, thrombocytopenia, and recurrent episodes of pneumonia. We report the first homozygous occurrence of the pathogenic variant Gly47Arg in the ERCC2 gene. Occurring homozygous, this variant was associated with COFS syndrome, leading to early death of the patient at the age of 21 months.
DNA 损伤修复是生命中的关键机制。核苷酸切除修复途径可保护细胞免受 DNA 损伤，涉及 XPD，这是一种 ATP 依赖性解旋酶，是多亚基蛋白复合物 TFIIH 的一部分。XPD 由切除修复交叉互补组 2 基因（ERCC2）编码。迄今为止，仅发表了三例由 ERCC2 突变引起的脑眼面骨骼综合征（COFS）患者。本报告描述了一名男孩 XPD 中的同源氨基酸变化 p.Gly47Arg。他表现为严重的小头畸形、精神运动发育迟缓、生长不良、皮肤光敏性、双侧听力缺陷和视神经萎缩、血小板减少症以及反复发生肺炎。我们报告了 ERCC2 基因中致病性变异 Gly47Arg 的首次纯合发生。该变体纯合发生，与 COFS 综合征相关，导致患者在 21 个月时死亡。
