Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Functions of the Thyroid-Stimulating Hormone on Key Developmental Features Revealed in a Series of Zebrafish Dyshormonogenesis Models

“…In mammals with a large number of exons and various exonic sizes separated by introns spanning a long range in genomic DNA, Tg transcripts are very heterogeneous due to the polymorphisms. Constitutive and alternative splicing in the human tg gene is complex [67]. In the present study, besides the tg transcript (long form), which is similar to the full-length tg mRNA deposited in GenBank, a very minor fraction of the total tg transcripts was detected as the alternative splicing form of the tg transcript (short form) in wild-type zebrafish (Figure 6E,F).…”

A novel mutation in intron 11 donor splice site, responsible of a rare genotype in thyroglobulin gene by altering the pre-mRNA splincing process. Cell expression and bioinformatic analysis

“…In particular, a missplicing of TG pre-mRNA due to a mutation in consensus donor or acceptor ss is known to induce a congenital goiter and hypothyroidism in humans. Exon skipping in the human TG gene can be caused by nucleotide Alzahrani et al, 2006;Bruellman et al, 2020b;Chen et al, 2018;Citterio et al, 2015, de Filippis et al, 2017Fu et al, 2016a, Gutnisky et al, 2004Hermanns et al, 2013Hu et al, 2016, Ieiri et al 1991Makretskaya et al, 2018;Medeiros-Neto et al, 1996;Narumi et al, 2011;Nicholas et al, 2016;Niu et al, 2009;Pardo et al, 2008Pardo et al, , 2009Peteiro-Gonzalez et al, 2010;Rubio et al, 2008;Targovnik et al, 1995Targovnik et al, , 2001Targovnik et al, , 2012Watanabe et al, 2019;Zou et al, 2018]. The usefulness of splicing reporter minigene assays has been shown to be a good approach to determine the effect of the variants on the splicing process [Bonnet et al, 2008;Tournier et al, 2008] when is difficult to obtain RNA from patients' tissues.…”

“…The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. During the last decades, two hundred twenty-seven variants in the human TG gene have been reported associated with congenital goiter and also endemic and nonendemic goiter: 26 splice site variants (19 in the donor splice site and 7 in the acceptor splice site), 42 nonsense variants, 130 missense variants (18 located at in the wild type cysteine residues, 7 originating new cysteine residues, 27 in the ChEL-homology domain and 78 located along the remaining TG monomer), 5 duplications (4 singles and 1 multiple), 2 insertion (1 multiple and 1 involving a large number of nucleotides), 21 deletions (13 singles, 4 multiples and 4 involving a large number of nucleotides) and 1 imperfect DNA inversion [Abdul-Hassan et al, 2013;Agretti et J o u r n a l P r e -p r o o f Alzahrani et al, 2006;Baryshev et al, 2004;Bruellman et al, 2020aBruellman et al, , 2020bBrust et al, 2011;Cangul et al, 2014;Caputo et al, 2007aCaputo et al, , 2007bCaron et al, 2003;Chen et al, 2018;Citterio et al, 2011Citterio et al, , 2013aCitterio et al, , 2013bCitterio et al, , 2015de Filippis et al, 2017;Fan et al, 2017;Fu et al, 2016aFu et al, , 2016bGutnisky et al, 2004;Heo et al, 2019;Hermanns et al, 2013;Hishinuma et al, 1999Hishinuma et al, , 2005Hishinuma et al, , 2006Hu et al, 2016;Ieiri et al, 1991;Jiang et al, 2016;Kahara et al, 2012;Kanou et al, 2007;Kim et al, 2008;Kitanaka et al, 2006;Liu et al, 2012;Lof et al, 2016;…”

Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism

“…The diagnostic criteria for TG defect is: intact iodide trapping, negative perchlorate discharge test and low serum TG levels. To date, one hundred seventeen mutations in the human TG gene have been identified and characterized associated to thyroid diseases: 19 splice site mutations, 23 nonsense mutations, 57 missense mutations, 13 deletions, 4 insertions or duplication and 1 M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 7 imperfect DNA inversion (Abdul-Hassan et al, 2013;Agretti et al, 2013;Alzahrani et al, 2006;Baryshev et al, 2004;Brust et al, 2011;Cangul et al, 2014;Caputo et al, 2007aCaputo et al, , 2007bCaron et al, 2003;Citterio et al, 2011Citterio et al, , 2013aCitterio et al, , 2013bCitterio et al, , 2015Corral et al, 1993;Fu et al, 2016;Gonzalez-Sarmiento et al, 2001;Gutnisky et al, 2004;Hermanns et al, 2013;Hishinuma et al, 1999Hishinuma et al, , 2005Hishinuma et al, , 2006Hu et al, 2016;Ieiri et al, 1991;Jiang et al, 2016;Kahara et al, 2012;Kanou et al, 2007;Kim et al, 2008;Kitanaka et al, 2006;Liu et al, 2012;Lof et al, 2016;Machiavelli et al, 2010;Medeiros-Neto et al, 1996;Mittal et al, 2016;Moya et al, 2011;Narumi et al, 2011;Nicholas et al, 2016;Niu et al, 2009;Pardo et al, 2008…”

“…On the other hand, we present a cohort analysis to assess the nature and frequency of TG mutations in 48 patients from 31 families with CH due to a TG defects, including the 7 families analysed in the present work. The majority of them reported by our laboratory over the last 2 decades and previously published (Caputo et al, 2007a(Caputo et al, , 2007bCaron et al, 2003;Citterio et al, 2011Citterio et al, , 2013aCitterio et al, , 2013bCitterio et al, , 2015Gutnisky et al, 2004;Machiavelli et al, 2010;Rivolta et al, 2005;Targovnik et al, 1993Targovnik et al, , 1995Targovnik et al, , 2001Targovnik et al, , 2010bTargovnik et al, , 2012. The baseline clinicopathologic characteristics and mutations are listed in Table 3.…”