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Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor ‐γ ( PPARG ) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C ( LMNA ) mutations
Author(s) -
Demir T.,
Onay H.,
Savage D. B.,
Temeloglu E.,
Uzum A. K.,
Kadioglu P.,
Altay C.,
Ozen S.,
Demir L.,
Cavdar U.,
Akinci B.
Publication year - 2016
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13061
Subject(s) - peroxisome proliferator activated receptor gamma , lmna , medicine , endocrinology , insulin resistance , lipodystrophy , missense mutation , mutation , genetics , diabetes mellitus , biology , peroxisome proliferator activated receptor , receptor , gene , immunology , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load
Aims To describe the phenotype associated with a novel heterozygous missense PPARG mutation discovered in a Turkish family and to compare the fat distribution and metabolic characteristics of subjects with the peroxisome proliferator activator receptor ‐γ ( PPARG ) mutation with those of a cluster of patients with familial partial lipodystrophy with classic codon 482 Lamin A/C ( LMNA ) mutations. Methods The study involved four subjects with familial partial lipodystrophy who had a novel PPARG mutation (H449L) and six subjects with classic codon 482 LMNA mutations (R482W). Results Compared with subjects with LMNA R482W mutation, fat loss was generally less prominent in subjects with the PPARG H449L mutation. Partial fat loss was limited to the extremities, whilst truncal fat mass was preserved. The PPARG H449L mutation was associated with insulin resistance, hypertriglyceridaemia and non‐alcoholic fatty liver disease in all affected subjects, but the severity was variable. Three out of four mutation carriers had overt diabetes or impaired glucose tolerance. Pioglitazone therapy in these three individuals resulted in a modest improvement in their metabolic control, and regular menstrual cycles in the two female subjects. Conclusions We suggest that relatively modest fat loss in patients with PPARG mutations may render the recognition of the syndrome more difficult in routine clinical practice. The PPARG H449L mutation is associated with insulin resistance and metabolic complications, but their severity is variable among the affected subjects.