Fig. 4.

Patient data and mutation analysis. (A) Family of index patient V39/02: Individuals with VCFS are shaded; circles symbolize females; squares symbolize males; and crossed symbols represent deceased family members. ?, no information available. (B) Shown at the top is a schematic representation of alternatively spliced TBX1 transcripts (TBX1A, TBX1B, TBX1C); arrows indicate position of known frameshift mutations in TBX1C; green boxes depict TBX1 coding sequences; and gray boxes depict UTRs. Shown at the bottom is a DNA sequence of a patient with the 1320–1342del23bp mutation (upper panel) and the wild-type TBX1 sequence in an unrelated individual (lower panel); the position of the mutation is boxed. (C) Subcellular localization of wild-type and mutant TBX1 constructs expressed in U2-OS cells. hTbx1, wild-type TBX1; 1320–1342del, del23bp mutation described here; G145R, predicted null mutation; 1250delC, point mutation described by Yagi et al. (26). Constructs were detected with anti-TBX1 antibody. Cell nuclei were stained with DAPI. (D) Transcriptional activation of the CAT reporter gene by wild-type and mutant TBX1. Significant differences in transcriptional activation between wild-type TBX1 and a TBX1 construct are indicated by ∗∗∗ (P ≤ 0.001). Data were normalized for transfection efficiency and depicted as average values ± SEM.