Mutational analysis of Peroxiredoxin IV: exclusion of a positional candidate for multinodular goitre

• Main Authors: Bonifazi Emanuela (Author), Filetti Sebastiano (Author), Arturi Franco (Author), Amati Francesca (Author), D'Apice M Rosaria (Author), Capon Francesca (Author), Giardina Emiliano (Author), Pucci Sabina (Author), Conte Chiara (Author), Novelli Giuseppe (Author)
• Format: Book
• Published: BMC, 2002-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>Multinodular goitre (MNG) is a common disorder characterised by an enlargement of the thyroid, occurring as a compensatory response to hormonogenesis impairment. The incidence of MNG is dependent on sex (female:male ratio 5:1) and several reports have documented a genetic basis for the disease. Last year we mapped a MNG locus to chromosome Xp22 in a region containing the peroxiredoxin IV (Prx-IV) gene. Since Prx-IV is involved in the removal of H₂O₂ in thyroid cells, we hypothesize that mutations in Prx-IV gene are involved in pathogenesis of MNG.</p> <p>Methods</p> <p>Four individuals (2 affected, 2 unrelated unaffected) were sequenced using automated methods. All individuals were originated from the original three-generation Italian family described in previous studies. A Southern blot analysis using a Prx-IV full-length cDNA as a probe was performed in order to exclude genomic rearrangements and/or intronic mutations. In addition a RT-PCR of PRX-IV was performed in order to investigate expression alterations.</p> <p>Results</p> <p>No causative mutations were found. Two adjacent nucleotide substitutions were detected within introns 1 and 4. These changes were also detected in unaffected individuals, suggesting that they were innocuous polymorphisms. No gross genomic rearrangements and/or restriction fragment alterations were observed on Southern analysis. Finally, using RT-PCR from tissue-specific RNA, no differences of PRX-IV expression-levels were detected between affected and unaffected samples.</p> <p>Conclusions</p> <p>Based on sequence and genomic analysis, Prx-IV is very unlikely to be the MNG2 gene.</p>

Item Description

10.1186/1471-2350-3-5
1471-2350