Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis
Abstract Background 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 spectr...
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doaj-6ee72999fdbd46ada582876a50c577ad2020-11-24T23:59:38ZengBMCClinical Diabetes and Endocrinology2055-82602018-03-01411610.1186/s40842-018-0058-3Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositisMelis Sahinoz0Shafaq Khairi1Ashley Cuttitta2Graham F. Brady3Amit Rupani4Rasimcan Meral5Marwan K. Tayeh6Peedikayil Thomas7Meredith Riebschleger8Sandra Camelo-Piragua9Jeffrey W. Innis10M. Bishr Omary11Daniel E. Michele12Elif A. Oral13Faculty of Medicine, Hacettepe UniversityMetabolism Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan and Brehm Center for DiabetesDepartment of Molecular and Integrative Physiology, University of MichiganDivision of Gastroenterology, Department of Internal Medicine, University of MichiganDivision of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics and Communicable Diseases, University of MichiganMetabolism Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan and Brehm Center for DiabetesDivision of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics and Communicable Diseases, University of MichiganDivision of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics and Communicable Diseases, University of MichiganDivision of Pediatric Rheumatology, Department of Pediatrics and Communicable Diseases, University of MichiganPathology Department, University of MichiganDivision of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics and Communicable Diseases, University of MichiganDepartment of Molecular and Integrative Physiology, University of MichiganDepartment of Molecular and Integrative Physiology, University of MichiganMetabolism Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan and Brehm Center for DiabetesAbstract Background 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. Case presentation 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. Conclusions 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.http://link.springer.com/article/10.1186/s40842-018-0058-3LaminopathiesMyositisLMNAWhole exome sequencingP.T10IMuscle biopsy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis Clinical Diabetes and Endocrinology Laminopathies Myositis LMNA Whole exome sequencing P.T10I Muscle biopsy |
author_facet |
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 |
author_sort |
Melis Sahinoz |
title |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis |
title_short |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis |
title_full |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis |
title_fullStr |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis |
title_full_unstemmed |
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis |
title_sort |
potential association of lmna-associated generalized lipodystrophy with juvenile dermatomyositis |
publisher |
BMC |
series |
Clinical Diabetes and Endocrinology |
issn |
2055-8260 |
publishDate |
2018-03-01 |
description |
Abstract Background 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. Case presentation 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. Conclusions 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. |
topic |
Laminopathies Myositis LMNA Whole exome sequencing P.T10I Muscle biopsy |
url |
http://link.springer.com/article/10.1186/s40842-018-0058-3 |
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