Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis

Clinical Diabetes and Endocrinology - Tập 4 - Trang 1-6 - 2018
Melis Sahinoz1, Shafaq Khairi2, Ashley Cuttitta3, Graham F. Brady4, Amit Rupani5, Rasimcan Meral2, Marwan K. Tayeh5, Peedikayil Thomas5, Meredith Riebschleger6, Sandra Camelo-Piragua7, Jeffrey W. Innis5,8, M. Bishr Omary3, Daniel E. Michele3, Elif A. Oral2
1Faculty of Medicine, Hacettepe University, Ankara, Turkey
2Metabolism Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan and Brehm Center for Diabetes, Ann Arbor, USA
3Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, USA
4Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA
5Division of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, USA
6Division of Pediatric Rheumatology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, USA
7Pathology Department, University of Michigan, Ann Arbor, USA
8Department of Human Genetics, University of Michigan, Ann Arbor, USA

Tóm tắt

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 LMNA 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 LMNA, 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 LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, 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.

Tài liệu tham khảo

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Clinical Diabetes and Endocrinology

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