Clinical Characteristics, Phenotype of Lipodystrophy and a Genetic Analysis of Six Diabetic Japanese Women with Familial Partial Lipodystrophy in a Diabetic Outpatient Clinic

Abstract

Objective Our aim was to examine the clinical characteristics and phenotype of lipodystrophy of six diabetic Japanese women with partial lipodystrophy (PL) who received a genetic analysis at a diabetic outpatient clinic. Methods We screened for PL using dual energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) among patients who had a reduced peripheral skinfold thickness at the diabetic outpatient clinic of Kusatsu General Hospital between August 2003 and August 2013. We performed a mutation analysis of candidate genes, including LMNA and PPARG, in two patients with PL and whole-exome sequencing in four patients with PL. Results We identified 15 patients with PL and performed a genetic analysis in 6 of them. They had no mutations in candidate genes known to be associated with familial partial lipodystrophy (FPLD). They all had near-complete loss of subcutaneous fat, particularly in the antero-lateral and posterior thigh region and the calf region. As almost all patients were characterized by fat loss in the lower limbs with abdominal fat accumulation, a high rate of positivity for a family history, diabetes, and an unknown genetic cause, we suspected they might have FPLD1. Some patients have shown relatively severe insulin resistance, while others have shown insulin deficiency. Four and one had severe atherosclerosis and liver cirrhosis, probably due to nonalcoholic steatohepatitis, respectively. Conclusion Almost all patients with PL identified in a diabetic outpatient clinic had subcutaneous fat loss in the lower limbs with excess truncal fat and might have had FPLD1.

Observation of p.R4810K, a Polymorphism of the Mysterin Gene, the Susceptibility Gene for Moyamoya Disease, in Two Female Japanese Diabetic Patients with Familial Partial Lipodystrophy 1

“…Previous studies reported that patients with FPLD1 may be predisposed to the development of severe atherosclerosis ( 8 , 10 , 12 , 13 ). Atherosclerosis has been considered to be caused by the accumulation of atherogenic risk factors, such as diabetes, dyslipidemia, hypertension, and low levels of serum adiponectin in patients with FPLD1.…”

“…The heterozygous variant p.R4810K in mysterin is found at a rate of >90% in Japanese patients with MMD (1). However, due to low genetic penetrance, carriers of this variant do not always develop MMD (1, 4); therefore, additional environmental and/or genetic factors are considered to be important for the development of MMD in Previous studies reported that patients with FPLD1 may be predisposed to the development of severe atherosclerosis (8,10,12,13). Atherosclerosis has been considered to be caused by the accumulation of atherogenic risk factors, such as diabetes, dyslipidemia, hypertension, and low levels of serum adiponectin in patients with FPLD1.…”

“…We confirmed the p.R4810K variant in mysterin in two patients (Patient 1 and 2) using direct sequencing. The clinical data from Patients 1 and 2 have been reported previously ( 8 - 10 ). The previous report showed that Patient 1 and Patient 2 might fit the category of familial partial lipodystrophy (FPLD)1 ( 8 , 10 ).…”

“…The clinical data from Patients 1 and 2 have been reported previously ( 8 - 10 ). The previous report showed that Patient 1 and Patient 2 might fit the category of familial partial lipodystrophy (FPLD)1 ( 8 , 10 ). Their basal and clinical characteristics are shown in Tables 1 and 2 , respectively.…”

“…We recently reported the clinical characteristics of 15 female Japanese patients with partial lipodystrophy (PL) in the outpatient clinic at Kusatsu General Hospital, who were diagnosed based on dual energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI) findings, and the clinical characteristics ( 8 ). We encountered some female Japanese diabetic patients with PL and MMD-like vascular lesions ( 8 - 10 ). This prompted us to examine whether mysterin mutations may be present in these patients.…”