case_images: PMC6631449_01
case_images: PMC6631449_02
case_images: PMC6631449_03
case_images: PMC6631449_04
case_images: 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)
case_images: 13044_2019_68_Fig1_HTML.jpg
case_images: PMC6631449_04_13044_2019_68_Fig1_HTML.jpg
case_images: Fig1
case_images: 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.
case_images: PMC6631449_05