Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant.
David Araújo-VilarAntia Fernandez-PomboBerta VictoriaAdrián Mosquera-OrgueiraSilvia Cobelo-GómezAna Castro-PaisÁlvaro Hermida-AmeijeirasLourdes LoidiSofía Sánchez-IglesiasPublished in: Journal of clinical medicine (2021)
Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromised.
Keyphrases
- body composition
- dual energy
- adipose tissue
- muscular dystrophy
- computed tomography
- case report
- genome wide
- bone mineral density
- copy number
- newly diagnosed
- resistance training
- end stage renal disease
- induced apoptosis
- real time pcr
- ejection fraction
- single cell
- genome wide identification
- gene expression
- early onset
- poor prognosis
- reactive oxygen species
- mental health
- magnetic resonance imaging
- transcription factor
- dna methylation
- oxidative stress
- cell death
- mass spectrometry