case_images: PMC5394421_01
case_images: PMC5394421_02
case_images: The pedigree and mutations of "TBX19 gene" detected in family members. (A) The pedigree of family carrying TBX19 mutations. (B) The image of heterozygous c.665delG (p.Arg222Lysfs*4) deletion in exon 4, which was inherited from the mother. The study was performed from the genomic DNA material. (C) The image of the same frameshift p.Arg222Lysfs*4 deletion studied from the RNA material of the index case and his carrier mother. (D) The image of known heterozygous c.856C>T mutation inherited from the father.
case_images: fendo-08-00064-g001.jpg
case_images: PMC5394421_02_fendo-08-00064-g001.jpg
case_images: F1
case_images: TBX19 allele and the abortion material was also analyzed molecularly. The pedigree was shown in Figure 1A. In the molecular analysis of the index case, a novel heterozygous c.665delG (p.Arg222Lys*4) variation in exon 4 (Figures 1B,C) and pathologic heterozygous c.856C>T (p.Arg286Ter) variation in exon 6 (Figure 1D) of the TBX19 gene instead of a c.665delG variant, because of the consecutive GG repeat at the exon-intron boundary. Therefore, further molecular analyses were performed at the mRNA level to gather information about the location of the variation (the last nucleotide of exon 4 or the first nucleotide of intron 4) and to identify a possible splicing effect. The mRNA analyses revealed that the real variation was c.665delG (p.Arg222Lysfs*4) and that it was a novel exonic frameshift mutation in spite of the splice site mutation (Figure 1C). The other c.856C>T substitution was a nonsense variant predicted to result in the substitution of an arginine by a premature stop codon at position 286 in the protein (p.Arg286Ter) (Figure 1D). Molecular analysis revealed that the mother was a carrier of the c.665delG variation (Figures 1B,C) and the father was a carrier of the p.R286X mutation (Figure 1D).