Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation

• Published in: Hormone and metabolic research Vol. 35; no. 1; p. 29
• Main Authors: Araújo-Vilar, D, Loidi, L, Domínguez, F, Cabezas-Cerrato, J
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2003
• Subjects: Adolescent; Adult; Anthropometry; Arm - pathology; Codon - genetics; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; DNA - genetics; Exons - genetics; Female; Homeostasis - physiology; Humans; Lamin Type A - genetics; Lamin Type A - metabolism; Lipodystrophy - genetics; Lipodystrophy - metabolism; Lipodystrophy - pathology; Male; Muscle, Skeletal - pathology; Mutation - genetics; Pedigree; Phenotype; Sex Characteristics
• ISSN: 0018-5043; 1439-4286
• DOI: 10.1055/s-2003-38388

Phenotypic features appeared after puberty in female, but not male subjects with familial partial lipodystrophy (FPLD). We have studied anthropometrical, clinical, and metabolic gender differences in a Spanish family with FPLD resulting from a lamin A/C gene mutation, R482W. Genetic studies were carried out on 14 members of the family. In eleven heterozygous mutation carriers (6 men, 5 women), body composition was evaluated by bioelectric impedance analysis, skin-fold measurements were taken, and lipid profiles were drawn. Moreover, plasma glucose, insulin, and leptin were determined, and insulin resistance and beta cell response were evaluated using HOMA. Ten healthy women and 10 healthy men matched for age and body mass index were used as control group. Body composition was similar in these patients to normal people. However, skin-folds of extremities were thinner in FPLD women compared with those of control subjects, but not in men. The affected women, but not men, showed hypoleptinaemia, insulin resistance, and beta-cell hyperresponse compared with unaffected women. The lipid profile was normal in the young patients, irrespective of sex. Type 2 diabetes mellitus and hypertriglyceridaemia were detected in old and overweight patients only. In conclusion, molecular diagnosis allows us to demonstrate that women with FPLD present both adipose tissue and biochemical abnormalities early in life, and this did not happen in affected men.