Early B-cell transcription factor-2 defect as a novel cause of lipodystrophy: disruption of the adipose tissue character and integrity.
Maria Cristina Foss de FreitasDonatella GilioAndre Monteiro da RochaLynn PaisMelanie C O'LearyHeidi L RehmAdam NeidertMiriam S UdlerPatrick SealeElif A OralTae-Hwa ChunPublished in: medRxiv : the preprint server for health sciences (2024)
We report a novel cause of partial lipodystrophy associated with early B cell factor 2 ( EBF2 ) nonsense variant ( EBF2 8:26033143 C>A, c.493G>T, p.E165X) in a patient with an atypical form of partial lipodystrophy. The patient presented with progressive adipose tissue loss and metabolic deterioration at pre-pubertal age. In vitro and in vivo disease modeling demonstrates that the EBF2 variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34 + cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, this EBF2 p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.
Keyphrases
- adipose tissue
- extracellular matrix
- induced apoptosis
- insulin resistance
- transcription factor
- case report
- cell cycle arrest
- high fat diet
- multiple sclerosis
- oxidative stress
- gene expression
- endoplasmic reticulum stress
- type diabetes
- bone marrow
- metabolic syndrome
- acute myeloid leukemia
- signaling pathway
- cell death
- dna binding
- pi k akt
- nk cells