Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cold Spring Harb Mol Case Stud. 2020 Aug 25;6(4). doi: 10.1101/mcs.a005165. Print 2020 Aug.
Pathogenic variants in the XPC complex subunit, DNA damage recognition, and repair factor () are the cause of xeroderma pigmentosum, group C (MIM: 278720). Xeroderma pigmentosum is an inherited condition characterized by hypersensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer due to a defect in nucleotide excision repair (NER). Here we describe an individual with a novel missense variant and deletion of exons 14-15 in presenting with a history of recurrent melanomas. The proband is a 39-yr-old female evaluated through the Mayo Clinic Department of Clinical Genomics. Prior to age 36, she had more than 60 skin biopsies that showed dysplastic nevi, many of which had atypia. At age 36 she presented with her first melanoma in situ, and since then has had more than 10 melanomas. The proband underwent research whole-exome sequencing (WES) through the Mayo Clinic's Center for Individualized Medicine and a novel heterozygous variant of uncertain significance (VUS) in (c.1709T > G, p.Val570Gly) was identified. Clinical confirmation pursued via gene sequencing and deletion/duplication analysis of revealed a pathogenic heterozygous deletion of ∼1 kb within , including exons 14 and 15. Research studies determined the alterations to be in Although variants in generally result in early-onset skin cancer in childhood, the proband is atypical in that she did not present with her first melanoma until age 36. Review of the patient's clinical, pathological, and genetic findings points to a diagnosis of delayed presentation of xeroderma pigmentosum.
XPC 复合物亚基、DNA 损伤识别和修复因子 () 的致病变异是着色性干皮病，C 组（MIM：278720）的病因。着色性干皮病是一种遗传性疾病，其特征为对紫外线（UV）照射敏感，由于核苷酸切除修复（NER）缺陷，皮肤癌风险增加。在这里，我们描述了一名个体，其携带一种新的错义变异和 14-15 外显子缺失，表现为复发性黑色素瘤病史。先证者是一名 39 岁女性，在梅奥诊所临床基因组学部接受评估。在 36 岁之前，她进行了 60 多次皮肤活检，显示发育不良痣，其中许多具有异型性。36 岁时，她首次出现原位黑色素瘤，此后已超过 10 次黑色素瘤。先证者通过梅奥诊所个体化医学中心进行了研究全外显子组测序（WES），并在 （c.1709T > G，p.Val570Gly）中发现了一种意义未明的杂合变异体（VUS）。通过 基因测序和 缺失/重复分析进行临床确认，发现 内存在约 1kb 的杂合致病性缺失，包括外显子 14 和 15。研究确定该改变为 虽然 中的变异通常导致儿童期早发性皮肤癌，但该先证者并不典型，因为她直到 36 岁才首次出现黑色素瘤。回顾患者的临床、病理和遗传发现，提示诊断为着色性干皮病迟发表现。
