Viewing Study NCT04578379



Ignite Creation Date: 2024-05-06 @ 3:15 PM
Last Modification Date: 2024-10-26 @ 1:46 PM
Study NCT ID: NCT04578379
Status: COMPLETED
Last Update Posted: 2020-10-08
First Post: 2020-10-01

Brief Title: Insulin Regulated Amino Peptidase in Patients With Familial Lipodystrophy of DUNNIGAN
Sponsor: Centre Hospitalier Universitaire de la Réunion
Organization: Centre Hospitalier Universitaire de la Réunion

Study Overview

Official Title: Interest of the IRAP Insulin Regulated Amino Peptidase Marker to Assess the Levels of Insulin Resistance in a Cohort of Insulin-resistant Subjects Due to DUNNIGAN Lipodystrophy
Status: COMPLETED
Status Verified Date: 2020-10
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: IRAP-DUN
Brief Summary: Familial Partial Lipodystrophy type 2 FPLD2 is a heterogeneous group of rare lipodystrophy due to autosomal dominant mutation in LMNA encoding Lamin AC Lamins A and C form with the B-type lamins the lamina network underlying the nuclear envelope Lamins are major components that provide structural and mechanical stability for the nucleus ubiquitously Lamins are also key epigenetic regulator Mutations in LMNA are involved in different inherited pathologies as Emery-Dreifuss muscular Dystrophy Limb Girdle muscular dystrophy dilated cardiomyopathy and conduction system disease Charcot Marie Tooth Disorder type 2 mandibuloacral dysplasia Hutchinson Gilford progeria and Dunnigan-type-familial partial lipodystrophy FPLD2

Inherited lipodystrophy prevalence is reported around 13 to 10 cases per million worldwide and FPLD2 is the most frequent of all Nevertheless recent reports with systematic screening in all non-obese patients with type 2 diabetes or metabolic syndrome found higher prevalence of lipodystrophy up to 17000 subjects FPLD2 remain a rare group of disease and only relatively small and heterogeneous cohorts of patients are reported For this reason it is difficult to fully decipher all aspects of this rare group of diseases The typical FPLD2 is associated with missense mutation affecting the arginin residue in position 482 pR482QpR482WpR482L Patients harbouring mutation in other spot are considered to have atypical lipodystrophy The typical FPLD2 start around puberty with progressive subcutaneous fat loss in upper limbs gluteo-femoral adipose tissue and trunk and fat accumulation in the cervicofacial area neck upper trunk labia majora and visceral fat Resulting from the inability to store fat patients affected by inherited lipodystrophy develop severe metabolic syndrome and its complications type 2 diabetes DT2 dyslipidaemia nonalcoholic fatty liver disease NAFLD and premature cardiovascular disease CVD

In 2006 a specific mutation of LMNA has been described in a patient originated from La Réunion living in France mainland To date this mutation have only been reported in patient native from La Réunion and is called Reunionese mutation and consist in a G insertion after nucleotide 5670 codon 654 in the prelamin-A-specific exon 11 g5670_5671insG pT655fsX49 that lead to a longer and non farnelysated prelamin A lacking the C-terminal CSIM motif As a result nonfarnelysated mutated prelamin A accumulated in the cells leading to oxidative stress and premature cell senescence The Reunionese mutation is expressed in 2 forms either homozygous or heterozygous Homozygous patients present with more severe phenotype and cardiac laminopathy

The aim of our study is to update the characterization of the patients diagnosed with the Reunionese mutation The investigators report here the largest cohort of patient with FPLD2 due to one single LMNA mutation either homozygous or heterozygous
Detailed Description: The investigators systematically reviewed the medical records of patients with a diagnosis of genetically confirmed FPLD at Reunion University Hospital La Réunion France from 2006 beginning of the screening for lipodystrophy to 2020 Due to the high prevalence of lipodystrophy in our island and to follow the recommendations in follow up a specific check-up is organized in our centre since 2016 For this study the investigators collected the data from patients who carried the same LMNA Reunionese mutation pT655fsX49 and who benefited a complete check-up in our centre since 2016 Between 2006 and 2020 97 patients were diagnosed with FPLD at Reunion University Hospital Three different mutations were diagnosed 85 subjects carried the Reunionese mutation LMNA pT655fsX49 70 heterozygous and 15 homozygous 8 carried the mutation LMNA pR582H and 3 subjects carried a mutation of PPARγ Among the carrier of the mutation LMNA pT655fsX49 70 subjects benefit a recent follow up with complete examination 61 heterozygous HTZ and 9 homozygous HMZ and 4 deceased all carrier of the homozygous form

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None