Whole exome sequencing revealed de novo heterozygous LMNAp.T10I mutation, indicating generalized lipodystrophy-associated progeroid syndrome, which is a newly identified subtype of atypical progeroid syndrome characterized by severe metabolic abnormalities.
Compared with other patients with APS, those with the heterozygous LMNAp.T10I mutation were younger in age but had increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly, together with higher fasting serum insulin and triglyceride levels and lower serum leptin and high-density lipoprotein cholesterol levels.
Our observations suggest that mutant lamin C disrupts its interaction with other cellular proteins resulting in generalized lipodystrophy due to defective development and maintenance of adipose tissue.
We report a case of a 12-yr-old boy referred to our unit with congenital generalized lipodystrophy and dilated cardiomyopathy related to a lamin gene mutation.
Mandibuloacral dysplasia (MAD) is an autosomal recessive progeroid disorder associated with type A (partial) or B (generalized) lipodystrophy and is due to mutations in lamin A/C (LMNA) or zinc metalloproteinase (ZMPSTE24) genes.
Common obesity and inherited lipodystrophies, rare disorders characterized by a partial (familial partial lipodystrophy; FPLD) or complete (congenital generalized lipodystrophy; CGL) lack of adipose tissue, are both associated with metabolic complications such as insulin resistance and type 2 diabetes.
Monogenic forms of insulin resistance, such as familial partial lipodystrophy, which results from mutations in either LMNA (encoding lamin A/C) or PPARG (encoding peroxisome proliferator-activated receptor gamma), and congenital generalized lipodystrophy, which results from mutations in either AGPAT2 (encoding 1-acylglycerol-3-phosphate O-acyltransferase) or BSCL2 (encoding seipin), can display features seen in the common metabolic syndrome.