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

Emiliano Giardina, Francesca Capon, M. Rosaria D'Apice, Francesca Amati, Franco Arturi, Sebastiano Filetti, Emanuela Bonifazi, Sabina Pucci, Chiara Conte, Giuseppe Novelli

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: Based on sequence and genomic analysis, Prx-IV is very unlikely to be the MNG2 gene.

Original languageEnglish
Article number5
JournalBMC Medical Genetics
Volume3
DOIs
Publication statusPublished - Jul 23 2002

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Peroxiredoxins
Goiter
Mutation
Thyroid Gland
Genes
Polymerase Chain Reaction
Inborn Genetic Diseases
Southern Blotting
Introns
Sequence Analysis
Nucleotides
Complementary DNA
Chromosomes
RNA
Incidence

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

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Mutational analysis of Peroxiredoxin IV : Exclusion of a positional candidate for multinodular goitre. / Giardina, Emiliano; Capon, Francesca; D'Apice, M. Rosaria; Amati, Francesca; Arturi, Franco; Filetti, Sebastiano; Bonifazi, Emanuela; Pucci, Sabina; Conte, Chiara; Novelli, Giuseppe.

In: BMC Medical Genetics, Vol. 3, 5, 23.07.2002.

Research output: Contribution to journalArticle

Giardina, E, Capon, F, D'Apice, MR, Amati, F, Arturi, F, Filetti, S, Bonifazi, E, Pucci, S, Conte, C & Novelli, G 2002, 'Mutational analysis of Peroxiredoxin IV: Exclusion of a positional candidate for multinodular goitre', BMC Medical Genetics, vol. 3, 5. https://doi.org/10.1186/1471-2350-3-5
Giardina, Emiliano ; Capon, Francesca ; D'Apice, M. Rosaria ; Amati, Francesca ; Arturi, Franco ; Filetti, Sebastiano ; Bonifazi, Emanuela ; Pucci, Sabina ; Conte, Chiara ; Novelli, Giuseppe. / Mutational analysis of Peroxiredoxin IV : Exclusion of a positional candidate for multinodular goitre. In: BMC Medical Genetics. 2002 ; Vol. 3.
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