Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes

Cicero, Alessandra Lo; Saidani, Manoubia; Allouche, Jennifer; Egesipe, Anne Laure; Hoch, Lucile; Bruge, Celine; Sigaudy, Sabine; Sandre-Giovannoli, Annachiara De; Lévy, Nicolas; Baldeschi, Christine; Nissan, Xavier

doi:10.1038/s41598-018-27165-y

Cited by 8 publications

(10 citation statements)

References 47 publications

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“…Nonetheless, the other cases were addressed from the rest of French territories or abroad, probably due to the unique availability of a large molecular screening in this kind of rare syndromes where, in some cases, large clinical overlaps can be observed. Additionally, this may be explained by the long-lasting involvement of our medical team in translational research and diagnosis of premature aging disorders, namely linked to Lamins A/C [1, 10, 13, 27, 57–62].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

Grelet

Blanck

Sigaudy

et al. 2019

Orphanet J Rare Dis

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BackgroundSegmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated.MethodsSince 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes.We analyzed the results obtained in 4 years on 66 patients issued from France and abroad.ResultsGlobally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives.ConclusionsHigh throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms (“Medicine France Genomics 2025” Plan), in families without molecular diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s13023-019-1189-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

Grelet

Blanck

Sigaudy

et al. 2019

Orphanet J Rare Dis

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“…To understand the relationship between pigmentation disorders and HGPS, Lo Cicero A, et al [16] derived two types of iPS cell lines from patients with HGPS and differentiated them into melanocytes. Compared with non-pathological cells, the HGPS melanocytes showed lower levels of melanin and a lower percentage of mature, fully pigmented melanosomes, thus demonstrating a direct role of progerin in the regulation of melanogenesis.…”

Section: Ipsc-derived Melanocytes As a Cell Model Of Hgpsmentioning

confidence: 99%

Recent research advances in disease models of Hutchinson-Gilford Progeria Syndrome

Yang¹

2022

Preprint

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Aging can cause many diseases, and aging research may help to elucidate the pathogenesis and identify suitable therapies for attenuating aging or alleviating aging-related diseases such as Hutchinson-Gilford progeria syndrome (HGPS). HGPS is a sporadic genetic premature disorder caused by a de novo point mutation in the LMNA gene encoding the intermediate filament proteins lamins A and C, typically resulting in a short lifespan (average age of 14.6 years). To date, there has been no effective therapy to cure it. In the past few decades, many scientists have focused on the development of disease models (such as iPSC, adult stem cell, and animal models) to uncover the underlying pathogenesis and find an effective therapy for HGPS. In this review, we summarize the recent advances in the disease models of HGPS, compare their advantages and disadvantages, and discuss the perspectives and challenges for these models, which may provide some clues for HGPS therapy.

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“…Over the years, thanks to the development of efficient protocols of differentiation for a growing number of cell types, embryonic stem cells (ES) and human induced pluripotent stem cells (hiPSC) have been reported as efficient alternative models to primary or genetically modified cells. Since their discovery in humans, in 1998 and 2007, the use of these cells has been explored for a broad range of applications, leading to the identification of new molecular mechanisms 36,37 , new pathological phenotypes [38][39][40][41] and the development of new therapies [42][43][44][45] (reviewed in Karagiannis et al, 2019) 46 . Although successfully applied for a number of genetic diseases, pathological modeling using pluripotent stem cells remained challenging for application to muscular disorders over almost a decade because of the lack of protocols for generating homogeneous populations of myotubes.…”

Section: Introductionmentioning

confidence: 99%

Skeletal muscle cells derived from induced pluripotent stem cells: A platform for limb girdle muscular dystrophies

Bruge

Geoffroy

Benabidès

et al. 2022

Preprint

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Limb girdle muscular dystrophies (LGMD), caused by mutations in 29 different genes, are the fourth most prevalent group of genetic muscle diseases, leading to progressive weakness and atrophy of the skeletal muscles. Although the link between LGMD and their genetic origins has been determined, LGMD still represent an unmet medical need. In this paper, we describe a platform for modeling LGMD based on the use of human induced pluripotent stem cells (hiPSC). Thanks to the self-renewing and pluripotency properties of hiPSC, this platform provides an alternative and renewable source of skeletal muscle cells (skMC) to primary, immortalized or overexpressing cells. We report that skMC derived from hiPSC express the majority of the genes and proteins causing LGMD. As a proof of concept, we demonstrate the importance of this cellular model for studying LGMDR9 by evaluating disease-specific phenotypes in skMC derived from hiPSC obtained from four patients.

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Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes

Cited by 8 publications

References 47 publications

Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

Recent research advances in disease models of Hutchinson-Gilford Progeria Syndrome

Skeletal muscle cells derived from induced pluripotent stem cells: A platform for limb girdle muscular dystrophies

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