scholarly journals 2287 ECG and echo characteristics in familial partial lipodystrophy: The impact of Lamin A variants

2018 ◽  
Vol 2 (S1) ◽  
pp. 41-42
Author(s):  
Abdelwahab J. Eldin ◽  
Rasimcan Meral ◽  
Adam H. Neidert ◽  
Diana Rus ◽  
Rita Hench ◽  
...  
Keyword(s):  
Pathogenic Variant ◽  
Lamin A ◽  
Lmna Gene ◽  
Partial Lipodystrophy ◽  
Severe Insulin Resistance ◽  
Inherited Cardiomyopathy ◽  
Increased Risk ◽  
Low Hdl ◽  
Familial Partial Lipodystrophy ◽  
The Impact

OBJECTIVES/SPECIFIC AIMS: Familial partial lipodystrophy (FPLD) is an inherited, rare syndrome characterized by selective absence of adipose tissue from extremities which is associated with severe insulin resistance, and metabolic dyslipidemia (with hypertriglyceridemia, and low HDL) Typically, 30%–50% of patients with FPLD demonstrate a pathogenic variant in Lamin A (LMNA) gene that is associated with inherited cardiomyopathy and arrhythmia syndromes. We inquired the prevalence of having abnormal ECGs and echocardiograms in FPLD and whether there is a difference in evaluated parameters with respect to genotype. METHODS/STUDY POPULATION: We conducted a retrospective review of an established a cohort of 58 patients (age range: 12–71, M/F 8/50) with FPLD. Demographic characteristics, genotype, fasting triglyceride, hemoglobin A1c, LDL, and HDL levels were collected; ECGs and echocardiograms were also interrogated. RESULTS/ANTICIPATED RESULTS: Out of 58 patients, 22 (38 %) displayed a pathogenic variant in the LMNA gene. In total, 71% of patients (41/58) had an abnormal ECG and echocardiogram; 40% (23/58) of the patients displayed an arrhythmia on the ECGs (13 in the patients with LMNA variants and 10 in the non-LMNA group). The likelihood of having an arrhythmia was significantly higher in the patients with LMNA variants versus those without (odds ratio of 3.4, CI: 1.1–10.6). DISCUSSION/SIGNIFICANCE OF IMPACT: The overall prevalence of abnormal ECHO and/or ECG is high at 45/58 (78 %) in FPLD. Patients with LMNA variants have a 3.4 times increased risk of developing cardiac arrhythmias compared to those without. We recommend vigilant, monitoring for cardiac disease in FPLD and for arrhythmias in patients with FPLD and LMNA variants.

scholarly journals Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin

2008 ◽  
Vol 159 (3) ◽  
pp. 347-353 ◽  
Author(s):  
A Gambineri ◽  
R K Semple ◽  
G Forlani ◽  
S Genghini ◽  
I Grassi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Lamin A ◽  
Ovary Syndrome ◽  
Partial Lipodystrophy ◽  
Severe Insulin Resistance ◽  
Insulin Resistant ◽  
Fat Deposits ◽  
Familial Partial Lipodystrophy

ContextDespite the very high prevalence of the polycystic ovary syndrome (PCOS), the underlying pathogenetic mechanism has remained obscure.ObjectiveTo determine the cause of two sisters' PCOS associated with severe insulin resistance.DesignClinical case report.MethodsTwo sisters who presented with hyperandrogenism and menstrual disorders in the context of PCOS, and were subsequently found to be severely insulin resistant. Physical examination revealed muscular hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, in spite of excess fat deposits in the face, neck and dorsocervical region. Known genes involved in familial partial lipodystrophy were screened. At the same time, metformin (1700 mg/day) was commenced. After 2–3 years of uninterrupted therapy, lack of clinical improvement led to the introduction of pioglitazone (30 mg/day).ResultsBoth sisters were found to be heterozygous for the R482Q mutation in the lamin A/C gene (LMNA) gene, establishing the definitive diagnosis as Dunnigan-type familial partial lipodystrophy complicated by severe insulin resistance and secondary PCOS. Treatment with pioglitazone resulted in progressive amelioration of insulin resistance, hyperinsulinaemia and hyperandrogenaemia. Menses also improved, with restoration of a eumenorrhoeic pattern, and the framework of ultrasound PCO was in complete remission.ConclusionsAssessment of insulin sensitivity and adipose tissue topography should be a key part of the initial evaluation of patients with PCOS. Identifying such forms of PCOS with monogenic insulin resistance as the primary pathogenic abnormality may have practical implications for therapy, since they respond to thiazolidinediones, but not to metformin.

scholarly journals Variable Expressivity in Type 2 Familial Partial Lipodystrophy Related to R482 and N466 Variants in the LMNA Gene

2021 ◽  
Vol 10 (6) ◽  
pp. 1259
Author(s):  
David Araújo-Vilar ◽  
Sofía Sánchez-Iglesias ◽  
Ana I. Castro ◽  
Silvia Cobelo-Gómez ◽  
Álvaro Hermida-Ameijeiras ◽  
...  
Keyword(s):  
Body Composition ◽  
Skinfold Thickness ◽  
Pathogenic Variant ◽  
The Other ◽  
Metabolic Abnormalities ◽  
Lmna Gene ◽  
Partial Lipodystrophy ◽  
Variable Expressivity ◽  
Familial Partial Lipodystrophy

Patients with Dunnigan disease (FPLD2) with a pathogenic variant affecting exon 8 of the LMNA gene are considered to have the classic disease, whereas those with variants in other exons manifest the “atypical” disease. The aim of this study was to investigate the degree of variable expressivity when comparing patients carrying the R482 and N466 variants in exon 8. Thus, 47 subjects with FPLD2 were studied: one group of 15 patients carrying the N466 variant and the other group of 32 patients with the R482 variant. Clinical, metabolic, and body composition data were compared between both groups. The thigh skinfold thickness was significantly decreased in the R482 group in comparison with the N466 group (4.2 ± 1.8 and 5.6 ± 2.0 mm, respectively, p = 0.002), with no other differences in body composition. Patients with the N466 variant showed higher triglyceride levels (177.5 [56–1937] vs. 130.0 [55–505] mg/dL, p = 0.029) and acute pancreatitis was only present in these subjects (20%). Other classic metabolic abnormalities related with the disease were present regardless of the pathogenic variant. Thus, although FPLD2 patients with the R482 and N466 variants share most of the classic characteristics, some phenotypic and metabolic differences suggest possible heterogeneity even within exon 8 of the LMNA gene.

scholarly journals Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1947
Author(s):  
Alice-Anaïs Varlet ◽  
Emmanuèle Helfer ◽  
Catherine Badens
Keyword(s):  
Mechanical Properties ◽  
Signaling Pathways ◽  
Metabolic Disorders ◽  
Lamin A ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Almost All ◽  
Type V

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis.

Spectrum of nuclear lamin A/C mutations and metabolic phenotypes in familial partial lipodystrophy

2000 ◽  
Vol 151 (1) ◽  
pp. 80
Author(s):  
RobertA. Hegele ◽  
CarolM. Anderson ◽  
Jian Wang ◽  
Henian Cao
Keyword(s):  
Lamin A ◽  
Partial Lipodystrophy ◽  
Metabolic Phenotypes ◽  
Nuclear Lamin ◽  
Familial Partial Lipodystrophy

The Impact of Familial Partial Lipodystrophy on Quality of Life from the Patients’ Perspective

2020 ◽  
Vol 14 (4) ◽  
pp. 590
Author(s):  
Elif Oral ◽  
Rob Halter ◽  
Caroline Crowson ◽  
Nandini Hadker ◽  
Brant Hubbard ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
The Impact ◽  
Patients Perspective

scholarly journals UNUSUAL PRESENTATIONS OF LMNA-ASSOCIATED LIPODYSTROPHY WITH COMPLEX PHENOTYPES AND GENERALIZED FAT LOSS: WHEN THE GENETIC DIAGNOSIS UNCOVERS NOVEL FEATURES

2020 ◽  
Vol 6 (2) ◽  
pp. e79-e85
Author(s):  
Natalia Xavier S. de Andrade ◽  
Suleyman Cem Adiyaman ◽  
Berna Demir Yuksel ◽  
Carla T. Ferrari ◽  
Abdelwahab Jalal Eldin ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Pathogenic Variant ◽  
The Body ◽  
Muscle Disease ◽  
Partial Lipodystrophy ◽  
Fat Loss ◽  
Pathogenic Variants ◽  
Complex Phenotypes ◽  
Familial Partial Lipodystrophy

Objective: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. Methods: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. Results: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. Conclusion: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.

Sign in / Sign up

Export Citation Format

Share Document