Inherited or de novo mutation affecting aspartate 18 of TREX1 results in either familial chilblain lupus or Aicardi–Goutières syndrome
Inherited or de novo mutation affecting aspartate 18 of TREX1 results in either familial chilblain lupus or Aicardi–Goutières syndrome
复制标题
影响 TREX1 的天冬氨酸 18 的遗传性或从头突变导致家族性冻疮狼疮或 AicardiâGoutières 综合征
DOI：
10.1111/j.1365-2133.2012.10813.x
复制
发表时间：
2012
影响因子：
10.3
通讯作者：
Lee-Kirsch MA
中科院分区：
文献类型：
--
作者：
Tüngler V;Silver RM;Walkenhorst H;Günther C;Lee-Kirsch MA
女士，家族性冻疮狼疮是一种罕见的皮肤红斑狼疮，其特征是寒冷引起的肢端皮肤病变。 1 它是由 TREX1（3￠修复核酸外切酶）或 SAMHD1（不育 α 基序和含 HD 的 1）突变引起的。 2-4 迄今为止仅描述了三个案例。这两个基因的双等位基因突变会导致 Aicardi-Goutieres 综合征 (AGS)，这是一种以系统性自身免疫症状为特征的炎症性脑病。 5, 6 我们报告了两例新的杂合 TREX1 突变病例，一例遗传性突变 (D18N) 导致家族性冻疮性狼疮，另一例为新发突变 (D18H)，在 AGS 背景下发生冻疮性狼疮。 患者 1 是一名 15 岁白人男孩，自婴儿期起就有寒冷诱发肢端皮肤病变史。 9 岁时，他的手指、脚趾、耳朵和鼻子出现溃疡性病变。此外，还发现左手小指发育不良（图 1a、b）。血细胞计数、尿液分析、红细胞沉降率以及 C3 和 C4 补体水平未见异常。抗核抗体（ANA）和冷球蛋白检测均为阴性。 14岁时，他的面部、手背和手腕出现了光敏性皮疹。重复 ANA 检测结果呈阴性。病变皮肤的组织学显示与红斑狼疮一致的空泡界面皮炎（图1c，d）。开始使用羟氯喹，皮疹消失。发作期间，他接受泼尼松治疗，并继续服用硝苯地平。父亲、祖父和同父异母的妹妹自童年起就报告了类似的皮肤症状。父亲和祖父的 ANA 滴度分别为 1:160 和 1:80。患者 2 是一对健康的非近亲结婚白人夫妇所生。出生体重、身长和头围均在正常范围内。经过一段平淡无奇的新生儿期后，在 4 个月大时注意到肌张力低下、肌张力障碍和头部生长减慢。除了肝酶升高外，实验室检查没有发现任何异常。常见围产期病毒感染检测结果呈阴性。脑成像显示未成熟的髓鞘形成、萎缩和基底神经节钙化。在脑脊液中测量到细胞增多和干扰素 (IFN)-o 水平升高至 50 IU mL)1。 5 岁时，孩子出现口腔炎和冻疮性狼疮，并在冬季加剧（图 1e-h）。自身抗体筛查显示核周抗中性粒细胞胞质抗体呈阳性。患者现年 9 岁，出现痉挛性四肢瘫痪和严重发育迟缓。
MADAM, Familial chilblain lupus is a rare form of cutaneous lupus erythematosus characterized by cold-induced skin lesions at acral locations. 1 It is caused by mutations in TREX1 (3¢ repair exonuclease) or SAMHD1 (sterile alpha motif and HD-containing 1). 2–4 To date only three cases have been described. Biallelic mutations in both genes cause Aicardi–Goutieres syndrome (AGS), an inflammatory encephalopathy featuring signs of systemic autoimmunity. 5, 6 We report two novel cases of heterozygous TREX1 mutations, one inherited mutation (D18N) leading to familial chilblain lupus and one de novo mutation (D18H) where chilblain lupus occurs within the context of AGS.Patient 1 is a 15-year-old white boy with a history of coldinduced acral skin lesions since infancy. At 9 years of age he presented with ulcerating lesions on fingers, toes, ears and nose. In addition, a hypoplastic left little finger was noted (Fig. 1a, b). Blood count, urinalysis, erythrocyte sedimentation rate, and C3 and C4 complement levels were unremarkable. Tests for antinuclear antibodies (ANA) and cryoglobulins were negative. At 14 years of age he developed a photosensitive rash on the face and the dorsum of hands and wrists. Repeated ANA testing was negative. Histology of lesional skin revealed a vacuolar interface dermatitis consistent with lupus erythematosus (Fig. 1c, d). Hydroxychloroquine was started and the rash resolved. He was treated with prednisone during flares and maintained on nifedipine. The father, paternal grandfather and paternal half-sister reported similar skin symptoms beginning in childhood. ANA titres of 1: 160 and 1: 80 were measured in the father and grandfather, respectively. Patient 2 was born to a healthy nonconsanguineous white couple. Birth weight, length and head circumference were within normal limits. Following an unremarkable neonatal period, hypotonia, dystonia and decelerated head growth were noticed at 4 months of age. Laboratory investigations were unremarkable except for elevated liver enzymes. Tests for common perinatal viral infections were negative. Brain imaging revealed immature myelination, atrophy, and basal ganglia calcification. Pleocytosis and a raised interferon (IFN)-o level of 50 IU mL) 1 were measured in cerebrospinal fluid. At 5 years of age the child developed stomatitis and chilblain lupus which exacerbated during winter (Fig. 1e–h). Screening for autoantibodies was positive for perinuclear antineutrophil cytoplasmic antibodies. At the current age of 9 years, the patient exhibits spastic tetraparesis and severe developmental delay.
影响因子：
9.8
作者：
Rice, Gillian;Newman, William G.;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
9.8
作者：
Rice, Gillian;Patrick, Teresa;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
9.8
作者：
Lee-Kirsch, Min Ae;Gong, Maolian;Linne, Maja
通讯作者：
Linne, Maja