PMC8397485_01
Variants in CH patients and their conservative analysis. (A) Genotypes of CH pedigrees; (B) Conservative analysis of seven novel variants in species. The reference sequences for TSHR, DUOX2, TG, and DUOXA2 in species are followed as: TSHR: Homo sapiens, NP_000360.2; Pan troglodytes, XP_009426511.1; Rattus norvegicus, NP_037020.2; Mus musculus, NP_035778.3; Bos taurus, NP_776631.1; Danio rerio, NP_001139235.1. DUOX2: Homo sapiens, NP_054799.4; Pan troglodytes, XP_009427327.1; Rattus norvegicus, NP_077055.2; Mus musculus, NP_001349684.1; Bos taurus, XP_005211958.1; Danio rerio, XP_002666953.2. TG: Homo sapiens, NP_003226.4; Pan troglodytes, XP_016815373.2; Rattus norvegicus, NP_112250.2; Mus musculus, NP_033401.2; Bos taurus, NP_776308.1; Danio rerio, NP_001316794.1. DUOXA2: Homo sapiens, NP_997464.2; Pan troglodytes, XP_001146826.2; Rattus norvegicus, NP_001178894.1; Mus musculus, NP_080053.1; Bos taurus, XP_002690989.1; Danio rerio, XP_017209762.1.
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F1
Durbin,) and annotated by ANNOVAR (http://annovar.openbioinformatics.org). A series of automatic tools (SIFT, Polyphen, MutationTaster, etc.) were used to predict the functional significance of variants (Table 2). DNA samples from family #1, #3, #4, #6, #7, #8, and #10 were verified further by Sanger sequencing (Supplementary Figure 1). Figure 1. Five causative genes, TSHR, TG, TPO, Variants were mostly transmitted from both parents, although two heterozygous variants of Case #2 and #9 were solely from the mother (Figure 1). W769*), was detected in Case #5 (Supplementary Figure 1). All the novel variants were localized in highly conserved regions of each protein (Figure 1) and predicted to be potential pathogenic variants by functional consequences annotation through multiple software (Table 2).