Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now.
Our study suggests that heterozygous variants that are predicted to result in PLIN1 haploinsufficiency are not a cause of familial partial lipodystrophy and should not be reported as disease-causing variants by diagnostic genetic testing laboratories.
Loss-of-function mutations in the PLIN1 gene were recently reported in patients with a novel subtype of familial partial lipodystrophy, designated as FPLD4.
In the acquired forms, genes such as LMNA, PPARG, CIDEC (cell-death-inducing DNA fragmentation factor a-like effector c) and PLIN1 are heavily involved in familial partial lipodystrophy (FPLD) type 2 (also known as the Dunnigan-Variety) and WRN along with RECQL5 in Werner Syndrome (WS).
We recently identified the first human loss-of-function mutations in PLIN1 in patients with a novel form of familial partial lipodystrophy, severe insulin resistance, diabetes, dyslipidaemia and fatty liver.