Characterization of Two Novel Mutations in the Apob Gene

Sponsor

Medical University Innsbruck (Other)

Overall Status

Unknown status

CT.gov ID

NCT03963037

Collaborator

(none)

Enrollment

Location

35.3

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The pilot study has the target to evaluate the outcomes of two novel mutations in the gene of Apolipoprotein B (ApoB). ApoB is the main part of the low-density lipoprotein (LDL). LDL is the main transporter of cholesterol from the liver to the periphery. The two novel mutations lead to a heavily truncated Apolipoprotein B. Therefore the patients show severely decreased ApoB and LDL-Cholesterol levels. The acquired disease is known as "Familial Hypobetalipoproteinemia". Beside the protection from cardiovascular disease due to decreased LDL-Cholesterol, patients tend to show elevated serum aminotransferases, fatty liver and occasional cases of cirrhosis and carcinoma.

To elucidate the differences in lipoprotein assembly the investigators aim to characterize the changes due to the mutations in the patients. Family members not carrying the mutations are the control group. The assessment includes lipoprotein fractionation, MRI scans of the liver and a thorough assessment of medical history of all patients to look for potential side effects of the mutation.

The only intervention needed for the study is to draw blood samples of every participant. The necessary positive vote from the ethics committee of the Medical University of Innsbruck is given.

Condition or Disease	Intervention/Treatment	Phase
Familial Hypobetalipoproteinaemia - Heterozygous Form Low-LDL-syndrome	Other: Blood draw

Study Design

Study Type:

Observational

Anticipated Enrollment :

16 participants

Observational Model:

Family-Based

Time Perspective:

Prospective

Official Title:

Characterization of Two Novel Truncating Mutations in the Apob Gene Leading to Hypobetalipoproteinemia: A Pilot Study

Actual Study Start Date :

Jan 24, 2019

Anticipated Primary Completion Date :

Jan 1, 2021

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Patients The family members of our two kindreds who carry the truncating mutation in the Apolipoprotein B gene.	Other: Blood draw Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.
Controls The family members of our two kindreds who are no carriers of the truncating mutation in the Apolipoprotein B gene.	Other: Blood draw Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.

Arm

Intervention/Treatment

Patients

The family members of our two kindreds who carry the truncating mutation in the Apolipoprotein B gene.

Other: Blood draw

Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.

Controls

The family members of our two kindreds who are no carriers of the truncating mutation in the Apolipoprotein B gene.

Other: Blood draw

Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.

Outcome Measures

Primary Outcome Measures

Difference in lipoprotein profiles [6 months]
Lipoprotein profiles are measured via Fast Protein Liquid Chromatography in both groups and compared.
Differences in amounts of liver fat [12 months]
Liver fat is non-invasive quantified by MRI scan
Differences in HDL-efflux [6 months]
Compare the results between groups of HDL-efflux assays