A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Cells Année : 2022

A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence

Résumé

Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in LMNB2 gene (c.700C > T p.(Arg234Trp)) in a female patient presenting early onset type II diabetes, hypertriglyceridemia, and android fat distribution. This mutation is rare in the general population (frequency 0.013% in GnomAD) and was predicted pathogenic by a set of pathogenicity prediction software. Patient-derived fibroblasts showed nuclear shape abnormalities and premature senescence features, which are two typical cellular phenotypes associated with laminopathies. Moreover, we observed an atypical aggregation of lamin B2 in nucleoplasm, which co-distributes with emerin and lamin A/C, along with an abnormal distribution of lamin A/C at the nuclear envelope. Finally, reducing lamin B2 expression level by siRNA targeted toward LMNB2 transcripts resulted in decreased nuclear anomalies and senescence-associated beta-galactosidase, suggesting a role of the mutated protein in the occurrence of the observed cellular phenotype. Altogether, these results suggest that mutations in lamin B2 could produce premature senescence and partial lipodystrophy features as observed with certain mutants of lamin A/C.
Fichier principal
Vignette du fichier
Cells2021_Varlet&al.pdf (4.01 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03586657 , version 1 (07-11-2022)

Licence

Paternité

Identifiants

Citer

Alice-Anaïs Varlet, Camille Desgrouas, Cécile Jebane, Nathalie Bonello-Palot, Patrice Bourgeois, et al.. A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence. Cells, 2022, 11 (1), pp.50. ⟨10.3390/cells11010050⟩. ⟨hal-03586657⟩
100 Consultations
32 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More