Characterization of Two Novel Mutations in the Apob Gene

• Conditions: Low-LDL-syndrome; Familial Hypobetalipoproteinaemia - Heterozygous Form
• Interventions: Other: Blood draw

• Registration Number: NCT03963037
• Lead Sponsor: Medical University Innsbruck

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-24
• Study First Submitted: 2019-05-22
• Study First Submitted QC: 2019-05-22
• Study First Posted: 2019-05-24
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-19
• Last Update Posted: 2020-02-20
• Primary Completion: 2021-01
• Study Completion: 2022-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Full legal age
• Written Informed Consent
• Diagnosed hypobetalipoproteinemia
• Exception of it are the controls
• Controls have to be family members
• Exclusion of a truncating mutation in the ApoB gene

Exclusion Criteria

• No diagnosed hypobetalipoproteinemia
• No truncating mutation in the Apo B gene
• Exception of it ar the controls

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Controls	Blood draw	The family members of our two kindreds who are no carriers of the truncating mutation in the Apolipoprotein B gene.
Patients	Blood draw	The family members of our two kindreds who carry the truncating mutation in the Apolipoprotein B gene.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Medical University Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria