Advances and Perspectives in Genetics of Congenital Thyroid Disorders Associated with Thyroglobulin Gene Mutations

HÉCTOR M. TARGOVNIK; CINTIA E. CITTERIO; SOFÍA SIFFO; CARINA M. RIVOLTA

Peertechz Journal of Biological Research and Development

Peertechz Publications Private Limited

Año: 2016 vol. 1 p. 62 - 70

2254-609X

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenitalhypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene isorganized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG genehave been identifi ed and characterized, originating structural changes in the protein that alter the normalprotein folding, assembly and biosynthesis of thyroid hormones: 19 splice site mutations, 23 nonsensemutations, 57 missense mutations, 13 deletions (9 single nucleotide deletions, 2 multiple nucleotidedeletions and 2 involving a large number of nucleotides), 4 single nucleotide insertions or duplicationand 1 imperfect DNA inversion. The p.R277*, p.R1511*, p.A2215D, p.R2223H and p.R2317* mutations arethe most frequently identifi ed TG mutations in Caucasian population, whereas c.274+2T>G, p.C1058R,p.C1245R and p.C1977S are the most common mutations in Asian population.TG mutations are inherited in an autosomal recessive manner and affected individuals are eitherhomozygous or compound heterozygous for gene mutations and the parents should be carriers of onethe TG mutation.New approaches including the use of new sequencing technology, will eclipse traditional methods ofdetecting mutations and will allow the quick identification of mutations in remote regions as well as thedetection of coexistence of multiple mutations in the same gene or in different thyroid genes.