Analysis of naturally occurring mutations in the human lipodystrophy protein seipin reveals multiple potential pathogenic mechanisms.

ABSTRACT:

Aims/hypothesis

In humans, disruption of the gene BSCL2, encoding the protein seipin, causes congenital generalised lipodystrophy (CGL) with severe insulin resistance and dyslipidaemia. While the causative gene has been known for over a decade, the molecular functions of seipin are only now being uncovered. Most pathogenic mutations in BSCL2 represent substantial disruptions including significant deletions and frameshifts. However, several more subtle mutations have been reported that cause premature stop codons or single amino acid substitutions. Here we have examined these mutant forms of seipin to gain insight into how they may cause CGL.

Methods

We generated constructs expressing mutant seipin proteins and determined their expression and localisation. We also assessed th

SUBMITTER: Sim MF 

PROVIDER: S-EPMC3824349 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature