Novel frameshift mutation causes early termination of the thyroxine-binding globulin protein and complete thyroxine-binding globulin deficiency in a Chinese family: A case report

Figure 1 Pedigree showing the genotype and thyroid function test results of the proband’s family. The results of thyroid function tests are aligned below each individual. Abnormal values are indicated in bold. Low values are marked with a downward arrow, and undetectable values are marked in red.

Figure 2 Schematic diagram of the DNA sequence for a portion of exons 1 and 3 of the TBG gene. The exons 1–4 region of the TBG gene and intron-exon boundaries were sequenced. For the variant names, the GenBank reference sequences NM_000354.5 and NP_000345.2 are used. Nucleotide numbering reflects cDNA numbering, with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence, according to HGVS guidelines (http://varnomen.hgvs.org/). The initiation codon is codon 1. Panel A displays a portion of exon 1 of the TBG gene showing the location of the insertional mutation. The upper part of the schematic diagram is the normal DNA sequence for this portion of exon 1. The middle and lower parts of the schematic diagram indicate the abnormal sequences of a portion of exon 1 of the TBG gene in two hemizygous sons (III-2 and III-3) and the heterozygous mother (II-1), respectively. A 19-nucleotide sequence was inserted between cDNA positions 381 and 382 (c.381_382insTTGCAGATAGGAAATG CCC) in exon 1. This mutation changes the phenylalanine at codon 135 to alanine and then encodes 19 amino acids, followed by an early termination codon at position 155, leading to premature termination of the thyroxine-binding globulin protein. The arrow indicates the start point of this mutation. The insertion sequence is located between the dotted lines. Panel B shows a schematic of a single nucleotide mutation in exon 3 of the TBG gene. A single nucleotide mutation (TTG→TTT) at codon 909 was identified in the proband’s father (II-2), but not in the other family members.