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Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome.
Mol Genet Metab. 2000 Dec; 71(4):539-44.MG

Abstract

Dunnigan-type familial partial lipodystrophy (FPLD; OMIM 151660) is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance. The findings may have relevance for common insulin resistance and for drug-associated lipodystrophies, whose molecular basis is unknown at present.

Authors+Show Affiliations

Robarts Research Institute, Ontario, London, Canada. robert.hegele@rri.on.ca

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11136544

Citation

Hegele, R A.. "Familial Partial Lipodystrophy: a Monogenic Form of the Insulin Resistance Syndrome." Molecular Genetics and Metabolism, vol. 71, no. 4, 2000, pp. 539-44.
Hegele RA. Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. Mol Genet Metab. 2000;71(4):539-44.
Hegele, R. A. (2000). Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. Molecular Genetics and Metabolism, 71(4), 539-44.
Hegele RA. Familial Partial Lipodystrophy: a Monogenic Form of the Insulin Resistance Syndrome. Mol Genet Metab. 2000;71(4):539-44. PubMed PMID: 11136544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. A1 - Hegele,R A, PY - 2001/1/4/pubmed PY - 2001/2/28/medline PY - 2001/1/4/entrez SP - 539 EP - 44 JF - Molecular genetics and metabolism JO - Mol Genet Metab VL - 71 IS - 4 N2 - Dunnigan-type familial partial lipodystrophy (FPLD; OMIM 151660) is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance. The findings may have relevance for common insulin resistance and for drug-associated lipodystrophies, whose molecular basis is unknown at present. SN - 1096-7192 UR - https://www.unboundmedicine.com/medline/citation/11136544/Familial_partial_lipodystrophy:_a_monogenic_form_of_the_insulin_resistance_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(00)93092-0 DB - PRIME DP - Unbound Medicine ER -