Neutral Lipid Storage Disease Associated with the &lt;b&gt;&lt;i&gt;PNPLA2&lt;/i&gt;&lt;/b&gt; Gene: Case Report and Literature Review

Samukawa, Makoto; Nakamura, Naoko; Hirano, Minoru; Morikawa, Miyuki; Sakata, Hanami; Nishino, Ichizo; Izumi, Rumiko; Suzuki, Naoki; Kuroda, Hiroshi; Shiga, Kiyoto; Saigoh, Kazumasa; Akiyama, Masashi; Kusunoki, Susumu

doi:10.1159/000508346

Cited by 5 publications

(2 citation statements)

References 16 publications

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“…Importantly, 1α,25-(OH) 2 D 3 signi cantly downregulated PNPLA2 in osteogenic media, a gene that encodes for adipose triglyceride lipase. Mutations in the PNPLA2 gene is associated with neutral lipid storage disease [40]. Further to this, results from our study may suggest that vitamin D treatment could play a role that can reduce the harmful pathophysiological effects involved in lipotoxicity in bone.…”

Section: Results 1α25-(oh) 2 D 3 -Regulates Genes Associated With Hmscs Function and Survivalsupporting

confidence: 56%

Elucidating the genetic effect of vitamin D on mesenchymal stem cell differentiation in vitro

Saedi

Debruin

Hayes

et al. 2022

Preprint

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The active form of vitamin D (1, Alpha 25-Hydroxyvitamin D3; [1α,25(OH)2D3]) is associated with multiple cellular processes, including bone formation. Severe vitamin D deficiency (as defined by serum 25-Hydroxyvitamin D <30nmol/L) typically results in growth retardation, rickets and osteomalacia. Conversely, 1α,25-(OH)2D3 treatment demonstrates anabolic effects on bone, which could be explained via its action on differentiating mesenchymal stem cells (MSCs). This study investigated the effect of 1α,25-(OH)2D3 on osteogenic and adipogenic differentiation of human MSCs (hMSC). We examined 12,000 human genes and expressed sequence tags on the array Human Genome U95A via Affymetrix DNA array. We confirmed genes with higher and lower expression by reverse transcription-polymerase chain reaction. We found that differentiating hMSC treated with 1α,25-(OH)2D3 exhibited a significantly higher expression of distinct osteogenic genes (CYP24A1, DSP, FBLN2, HYAL3, MN1 and TBCD) and adipogenic genes (Fibulin 2 [FBLN2], DSP and G0S2) when compared to undifferentiating hMSCs. In addition, FBLN2 showed a significantly higher expression when treated with 1α,25-(OH)2D3 in both adipogenic and osteogenic conditions. Meanwhile, CYP24A1, which is associated with 1α,25-(OH)2D3 degradation, had reduced expression in adipogenic compared to osteogenic and MSCs growth media. In summary, our gene array analysis identified a direct effect of 1α,25-(OH)2D3 on a set of genes required for hMSCs differentiation, thus improving our understanding of the effect of the active form on vitamin D on bone metabolism.

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Section: Results 1α25-(oh) 2 D 3 -Regulates Genes Associated With Hmscs Function and Survivalsupporting

confidence: 56%

Elucidating the genetic effect of vitamin D on mesenchymal stem cell differentiation in vitro

Saedi

Debruin

Hayes

et al. 2022

Preprint

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“…The typical age of symptoms onset is in the second or third decade, starting with slow progressive proximal limb weakness and atrophy, especially in shoulder girdle (70% of the cases) [ 6 ], although less pronounced pelvic girdle and distal musculature involvement are commonly present [ 6 ]. Cardiac pathology can occur lately in half of patients, usually observed in the fourth decade of life [ 6 ]. Hepatomegaly, diabetes mellitus and hypertriglyceridemia can also occur [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Neutral lipid storage disease with myopathy and myotonia associated to pathogenic variants on PNPLA2 and CLCN1 genes: case report

et al. 2023

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Background Neutral lipid storage disease with myopathy (NLSD-M) is an autosomal recessive disease that manifests itself around the 3rd to 4th decade with chronic myopathy predominantly proximal in the shoulder girdle. Clinical myotonia is uncommon. We will report a rare case of association of pathogenic variants on PNPLA2 and CLCN1 genes with a mixed phenotype of NLSD-M and a subclinical form of Thomsen’s congenital myotonia. Case presentation We describe a patient with chronic proximal myopathy, subtle clinical myotonia and electrical myotonia on electromyography (EMG). Serum laboratory analysis disclosure hyperCKemia (CK 1280 mg/dL). A blood smear analysis showed Jordan’s anomaly, a hallmark of NLSD-M. A genetic panel was collected using next-generation sequencing (NGS) technique, which identified two pathogenic variants on genes supporting two different diagnosis: NLSD-M and Thomsen congenital myotonia, whose association has not been previously described. Conclusions Although uncommon, it is important to remember the possibility of association of pathogenic variants to explain a specific neuromuscular disease phenotype. The use of a range of complementary methods, including myopathy genetic panels, may be essential to diagnostic definition in such cases.

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Identification of a novel mutation and genotype–phenotype relationship in MEGF10 myopathy

Fujii

Hirano

Terayama

et al. 2022

Neuromuscular Disorders

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Neutral Lipid Storage Disease Associated with the <b><i>PNPLA2</i></b> Gene: Case Report and Literature Review

Cited by 5 publications

References 16 publications

Elucidating the genetic effect of vitamin D on mesenchymal stem cell differentiation in vitro

Elucidating the genetic effect of vitamin D on mesenchymal stem cell differentiation in vitro

Neutral lipid storage disease with myopathy and myotonia associated to pathogenic variants on PNPLA2 and CLCN1 genes: case report

Identification of a novel mutation and genotype–phenotype relationship in MEGF10 myopathy

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