Identification of a New Gene Involved in Hereditary Lipodystrophy

NCT02056912 | Completed

• 1 other identifier: CHUBX 2013/13
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Human lipodystrophies (lipoD) represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial.3, 4 Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Acquired lipoD can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. The most common forms of lipoD are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Genetic forms are very uncommon: recessive generalized congenital lipoD result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipoD result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma. Importantly, LMNA mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. Molecular genetic bases of many rare forms of genetic lipoD remain to be elucidated.

Conditions

Lipodystrophy

Keywords

lipodystrophy; gene; inborn error of metabolism

Outcome Measures

Primary Outcomes (5)

• Additional mutation in the studied candidate gene XX

  Study's primary outcome

  6 months

• Altered lipids composition in blood red cells membranes

  Sub-study's primary outcome

  6 months

• Quantitative or qualitative variation of the protein encoded by the candidate gene in fibroblasts

  Sub-study's primary outcome

  6 months

• Dense deposits in fibroblasts cytoplasm

  Sub-study's primary outcome

  6 months

• Phospholipids anomalies in plasma

  Sub-study's primary outcome

  6 months

Study Arms (1)

Lipodystrophie Héréditaire

OTHER

Genetic: Amplification by PCR and direct sequencing on the entire coding sequence and intron-exons boundaries of the candidate gene; Biological: Perform blood cells and fibroblasts biochemical and immuno-labeled investigations

Interventions

Amplification by PCR and direct sequencing on the entire coding sequence and intron-exons boundaries of the candidate gene GENETIC

Lipodystrophie Héréditaire

Perform blood cells and fibroblasts biochemical and immuno-labeled investigations BIOLOGICAL

Performed only in the two index patients enrolled in the sub-study

Lipodystrophie Héréditaire

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study :
• Patients affected by lipoD
• No identified genetic cause of lipoD
• Child or adult
• DNA already available in the French reference laboratory for the genetic diagnosis of lipoD (laboratoire de Biochimie du CHU Saint-Antoine, Paris) or in the INSERM UMRS 938 laboratory, Faculté de médecine Pierre et Marie Curie Site Saint-Antoine, Paris
• Subject affiliated to the french Sécurité Sociale
• Signed consent obtained for the molecular diagnosis of lipoD.
• Sub-study:
• Signed consent obtained for this sub-study from both index patients

You may not qualify if:

• Study:
• Identified genetic cause of lipoD
• No signed consent by the patient
• Subject not affiliated to the french Sécurité Sociale.
• Sub-study:
• Absence of signed consent obtained for this sub-study from both index patients

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

Service de Génétique Médicale

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Lipodystrophy; Metabolism, Inborn Errors

Condition Hierarchy (Ancestors)

Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Marie-Laure VUILLAUME

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: February 6, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 14, 2015

Record last verified: 2015-01

Locations

FR (1)