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

We report a novel cause of partial lipodystrophy associated with early B cell factor 2 () nonsense variant ( 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. and disease modeling demonstrates that the variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34 cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, this p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.