Title |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis
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Published in |
Clinical Diabetes and Endocrinology, March 2018
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DOI | 10.1186/s40842-018-0058-3 |
Pubmed ID | |
Authors |
Melis Sahinoz, Shafaq Khairi, Ashley Cuttitta, Graham F. Brady, Amit Rupani, Rasimcan Meral, Marwan K. Tayeh, Peedikayil Thomas, Meredith Riebschleger, Sandra Camelo-Piragua, Jeffrey W. Innis, M. Bishr Omary, Daniel E. Michele, Elif A. Oral |
Abstract |
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.T10ILMNAvariant 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 inLMNA,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.T10ILMNAvariant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility thatLMNA, 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. |
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Switzerland | 1 | 50% |
United States | 1 | 50% |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 25% |
Other | 3 | 19% |
Student > Master | 2 | 13% |
Student > Doctoral Student | 1 | 6% |
Lecturer > Senior Lecturer | 1 | 6% |
Other | 1 | 6% |
Unknown | 4 | 25% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 25% |
Biochemistry, Genetics and Molecular Biology | 2 | 13% |
Neuroscience | 2 | 13% |
Immunology and Microbiology | 2 | 13% |
Nursing and Health Professions | 1 | 6% |
Other | 1 | 6% |
Unknown | 4 | 25% |