Chanarin-Dorfman syndrome: Genotype-Phenotype Correlation

Nur, Banu; Gençpınar, Pınar; Yüzbaşıoğlu, Ayşe; Emre, Serap; Mıhçı, Ercan

doi:10.1016/j.ejmg.2015.01.011

Cited by 31 publications

(30 citation statements)

References 15 publications

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“…A recent Turkish report on this question failed to detect any meaningful correlations [28]. In NLSD-M, an evaluation of residual enzymatic activity in vitro can predict the type of mutation and provides general information on the severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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BackgroundA small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases.ResultsDuring the clinical follow-up (range: 2–44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias.ConclusionThe genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases.

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Section: Discussionmentioning

confidence: 99%

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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“…Others have shown discordance between insulin resistance and tissue lipid deposition, such as in Chanarin-Dorfman Syndrome and genetic forms of hepatic steatosis (45,46).…”

Section: Discussionmentioning

confidence: 99%

Adipocyte JAK2 Mediates Growth Hormone-Induced Hepatic Insulin Resistance

Corbit

Camporez²,

Tran

et al. 2016

Preprint

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For nearly 100 years, Growth Hormone (GH) has been known to regulate insulin sensitivity and risk of diabetes. However, the tissue governing the effects of GH signaling on insulin and glucose homeostasis remains unknown. Excess GH reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is associated with increased adiposity, augmented insulin sensitivity, and protection from diabetes.Here we induce adipocyte-specific GHI through conditional deletion of Jak2 (JAK2A), an obligate transducer of GH signaling. Similar to whole-body GHI, JAK2A mice had increased adiposity and extreme insulin sensitivity. Loss of adipocyte Jak2 augmented hepatic insulin sensitivity and conferred resistance to diet-induced metabolic stress without overt changes in circulating fatty acids. While GH injections induced hepatic insulin resistance in control mice, the diabetogenic action was absent in JAK2A mice. Collectively, our results show that adipose tissue governs the effects of GH on insulin and glucose homeostasis. Further, we show that JAK2 mediates liver insulin sensitivity via an extra-hepatic, adipose tissue-dependent mechanism.

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“…Likewise, muscle-specific inactivation of CGI-58 in mice induces skeletal steatosis but only in oxidative muscle [61]. It is not surprising then that CGI-58 mutations produce lipid storage diseases, such as the Chanarin-Dorfman syndrome, which is characterized by neutral lipid accumulation in skeletal muscle and ichthyosis [62]. Interestingly, Xie et al found that diminished CGI-58 levels improve glucose tolerance and insulin sensitivity in mice fed with high-fat diet (HFD).…”

Section: Overview Of Lipid Metabolism In Healthy Skeletal Musclementioning

confidence: 99%

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

Morales

Bucarey

Espinosa

2017

Journal of Diabetes Research

129

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Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA) availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR). In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN) family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

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Chanarin-Dorfman syndrome: Genotype-Phenotype Correlation

Cited by 31 publications

References 15 publications

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Adipocyte JAK2 Mediates Growth Hormone-Induced Hepatic Insulin Resistance

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

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