Identification of a KEAP1 germline mutation in a family with multinodular goitre.

ABSTRACT:

Background

The familial clustering of multinodular goitres (MNGs) with a dominant mode of inheritance has been repeatedly reported. Linkage studies have revealed several genetic loci responsible for familial MNG; however, most of the causative variants remain unknown.

Methods and results

Through linkage analysis using single-nucleotide polymorphism markers, we identified a new MNG locus on 19p13.2-q12 in a five-generation Japanese MNG family. Subsequent mutation searches focusing on the candidate 25-Mb region of chromosome 19 identified a heterozygous mutation, c.879_880delinsA, p.Asp294Thr, fs*23, in exon 3 of the KEAP1, which plays a central role in the cytoprotection pathway against oxidative stress. Reverse transcriptase-PCR analysis showed low expression of wild type KE

SUBMITTER: Teshiba R 

PROVIDER: S-EPMC3665763 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature