The disorder is caused by biallelic loss-of-function variants in PLAAT3, a lipid modifying enzyme predominantly expressed in white adipose tissue. All variants that have been reported today are complete loss-of-function (LoF) variants (out-of-frame exon deletion, frameshift variant, nonsense variants). To date, no missense variants have been reported, though missense variant with LoF properties might also be disease-causing.
Since phenotypically there is overlap between the different hereditary lipodystrophy syndromes, exome or genome sequencing followed by gene panel analysis is recommended. Copy number variants should be assessed.
In the majority of patients hypertriglyceridemia and low leptin levels were seen in serum.
PLAAT3