Interestingly her mother, with a history of myocardial infarction and diabetes at the age of 46 but no oligomenorrhoea, was also found to harbour the same mutation (LMNAR482Q).
Mutations of the LMNA gene have been shown to cause an autosomal dominant form of insulin resistance with familial partial lipodystrophy (PLD), frequently accompanied by diabetes.
Pathophysiological mechanisms explaining how mutations in an unique gene could lead to such various phenotypes are still unknown, but probably involve alterations in cellular mechanical stress responses, in gene expression, and/or in post-translational maturation of lamin A. Familial Partial Lipodystrophy of the Dunnigan type (FPLD2), with specific features of pseudo-cushingoid lipodystrophy, marked insulin resistance and muscular hypertrophy, and a relatively homogeneous genotype, was thought, until recently, to be the only laminopathy causing diabetes.
The premature atherosclerosis of FPLD2 is probably related to characteristic proatherogenic metabolic disturbances such as dyslipidemia, hyperinsulinemia, hypertension, and diabetes.
The LMNA gene encoding two nuclear envelope proteins (lamins A and C [lamin A/C]) maps to chromosome 1q21 and has been associated with five distinct pathologies, including Dunnigan-type familial partial lipodystrophy, a condition that is characterized by subcutaneous fat loss and is invariably associated with insulin resistance and diabetes.
We reassessed the linkage with diabetes following adjustment for the LMNA3408C/T variant; adjustment for the effects of LMNA did not substantially modify the evidence for linkage.
We previously identified a novel mutation, namely LMNAR482Q, that was found to underlie Dunnigan-type partial lipodystrophy (FPLD) and diabetes in an extended Canadian kindred.