Sahinoz Melis, Khairi Shafaq, Cuttitta Ashley, Brady Graham F, Rupani Amit, Meral Rasimcan, Tayeh Marwan K, Thomas Peedikayil, Riebschleger Meredith, Camelo-Piragua Sandra, Innis Jeffrey W, Bishr Omary M, Michele Daniel E, Oral Elif A
1Faculty of Medicine, Hacettepe University, Ankara, Turkey.
2Metabolism Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan and Brehm Center for Diabetes, 1000 Wall Street, Room 5313, Ann Arbor, MI MI48105 USA.
Clin Diabetes Endocrinol. 2018 Mar 27;4:6. doi: 10.1186/s40842-018-0058-3. eCollection 2018.
Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome.
A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation.
This is a unique case with p.T10I variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that , and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.
青少年皮肌炎（JDM）是一种自身免疫性肌肉疾病，伴有皮肤表现和肌肉无力。至少10%的JDM患者会出现获得性脂肪营养不良。核纤层蛋白病由核纤层蛋白基因突变引起，涵盖多种疾病，包括肌肉营养不良和脂肪营养不良。p.T10I变异与全身性脂肪营养不良的一种表型相关，这种表型也被称为非典型早老综合征。
一名既往健康的女性在4岁时出现双侧下肢近端肌肉无力。根据其临床表现、实验室检查和磁共振成像（MRI），她被诊断为JDM。她出现了皮下脂肪减少，始于四肢并发展至全身。7岁时，她患有糖尿病、高甘油三酯血症、瘦素水平低，双能X线吸收法（DEXA）扫描显示体脂低，被诊断为获得性全身性脂肪营养不良（AGL）。全外显子测序（WES）揭示了一个杂合的c.29C>T；p.T10I错义致病变异，该变异编码核纤层蛋白A和C。肌肉活检证实为JDM而非肌肉营养不良，显示束周萎缩和血管周围单核细胞浸润。皮肤成纤维细胞的免疫荧光证实了核异型性和核碎裂。
这是一例独特的病例，p.T10I变异同时表现为JDM和AGL。这种共现引发了一个有趣的可能性，即 ，可能还有p.T10I，不仅在全身性脂肪营养不良的发生中，而且在青少年皮肌炎中可能都具有致病作用。有必要对更多核纤层蛋白病患者以及JDM患者进行仔细的表型特征分析。
