RT Journal Article
T1 Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant
A1 Araujo-Vilar, David
A1 Fernández Pombo, Antía
A1 Victoria Martínez, Berta
A1 Mosquera Orgueira, Adrián
A1 Cobelo Gómez, Silvia
A1 Castro Pais, Ana
A1 Hermida Ameijeiras, Álvaro
A1 Loidi, Lourdes
A1 Sánchez Iglesias, Sofía
K1 Type 2 familial partial lipodystrophy
K1 FPLD2
K1 LMNA
K1 T528M
AB 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
PB MDPI
YR 2021
FD 2021
LK http://hdl.handle.net/10347/25264
UL http://hdl.handle.net/10347/25264
LA eng
NO J. Clin. Med. 2021, 10(7), 1497; https://doi.org/10.3390/jcm10071497
NO This research was funded by the Instituto de Salud Carlos III and the European Regional Development Fund, FEDER (grant number PI081449), and an intramural grant from the Xunta de Galicia (grant number ED431B 2020/37). S.S.I. was awarded a Research Fellowship by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP)
DS Minerva
RD 23 abr 2026