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NCT Number: NCT02056912

Identification of a New Gene Involved in Hereditary Lipodystrophy

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service de Génétique Médicale

Bordeaux, 33076, France

About this study

The investigators have recently evaluated two sisters (index patients) affected by a syndrome associating diffuse leukoencephalopathy and partial lipoD. The investigators have analyzed numerous known genetic causes of leukodystrophies and lipoD but the investigators failed to identify a known cause for this syndrome which has never been previously reported. The investigators then switched their effort to analyses of exome using next generation sequencing in both affected sisters and their unaffected relatives (one sister and two parents). The investigators identified an excellent candidate gene with a homozygous missense mutation in both affected sisters. The investigators now aim to prove the involvement of this candidate gene in lipoD's determinism by a search of additional mutations in the candidate gene in a series of patients affected with lipoD (collaboration with Pr Capeau's Team) (LIPOGENE study) and by functional analyses performed in the two index patients on blood and skin samples (LIPOGENE sub-study).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

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

Genetic

Perform blood cells and fibroblasts biochemical and immuno-labeled investigations

Biological

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

Primary outcomes

  1. Additional mutation in the studied candidate gene XX

    Time frame: 6 months

    Study's primary outcome

  2. Altered lipids composition in blood red cells membranes

    Time frame: 6 months

    Sub-study's primary outcome

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

    Time frame: 6 months

    Sub-study's primary outcome

  4. Dense deposits in fibroblasts cytoplasm

    Time frame: 6 months

    Sub-study's primary outcome

  5. Phospholipids anomalies in plasma

    Time frame: 6 months

    Sub-study's primary outcome

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Official study title

Identification of a New Gene Involved in Hereditary Lipodystrophy - LIPOGENE

Acronym: LIPOGENE

Important dates

Study start
2014
Primary completion
2014
Study completion
2014
First posted
Feb 6, 2014
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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