Early B-cell transcription factor-2 defect as a novel cause of lipodystrophy: disruption of the adipose tissue character and integrity

Abstract

SummaryWe report a novel cause of partial lipodystrophy associated with early B cell factor 2 (EBF2) nonsense variant (EBF28:26033143 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 vitroandin vivodisease modeling demonstrates that theEBF2variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34+cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, thisEBF2p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.