PMC6631449_01
PMC6631449_02
PMC6631449_03
PMC6631449_04
Patient's pedigree and results from genetic testing. Whole exome sequencing identified a heterozygous "de novo" pathogenic variant NM_001252634.1(THRB):c.1012C > T changing evolutionary conserved amino acid Arg338 to Trp (p.Arg338Trp). The variant was not found in the healthy parents (I:1, I:2) and sister (II:1), both maternity and paternity was confirmed with microsatellite testing (data not shown)
13044_2019_68_Fig1_HTML.jpg
PMC6631449_04_13044_2019_68_Fig1_HTML.jpg
Fig1
THRB p.Arg228Trp) leading to RTH (Fig. 1). This variant has been described in more than 30 families/cases with RTH so far, and has not been described in the databases of human variation (dbSNP, 1000 genomes). The variant affects an evolutionary highly conserved amino acid, is predicted to be damaging/deleterious by in silico prediction tools (PolyPhen, SIFT), and in vitro studies have shown that this variant affects T3 binding to the thyroid hormone receptor.
PMC6631449_05