In Panel A, analysis by fluorescence in situ hybridization (FISH) was performed on interphase and metaphase spreads prepared from both fresh lymphocytes and lymphoblastoid cell lines, as described previously,⁷ and in all cases the results were the same. Shown is FISH analysis of Patient 1 with clones from within the region (CTA-208H19 and RP5-1186P10) that is commonly deleted in the Williams–Beuren syndrome (WBS) and from an area flanking that region (CTB-139P11 and cos207g3). Fluorescent signals are grouped into those from the normal chromosome 7 (N Chr 7) and from the duplicated chromosome 7 (Dup Chr 7). A schematic representation of the location of the probes on each chromosome is also shown. The chromosomes are oriented with the centromere at the top, and the low copy repeats (LCRs) are depicted as gray boxes. The probes are depicted in colors corresponding to the FISH image. The 1.5-Mb region of chromosome 7q11.23 that is commonly deleted in WBS is indicated. Panel B shows a map of the region of exchange in block B leading to duplication of the common 1.5-Mb WBS deletion region. Polymorphic microsatellite markers and genes from the WBS region are shown on the top. The unique sequence is depicted by gray lines, and the repetitive blocks that constitute the LCRs are depicted as black arrows, indicating their orientation on the chromosome. A detailed schematic representation of the entire 143-kb length of block B is also shown. The dotted arrow on the right shows that the last 38 kb is absent in the centromeric B block (B_c). The genomic structure of genes within the region is also shown. The genes are those encoding general transcription factor 2 I (GTF2I), neutrophil cytosolic factor 1 (NCF1), and GTF2I repeat domain containing protein 2 (GTF2IRD2). Functional copies of these genes are present in block B_m, and corresponding pseudogenes (P1 or P2) are present in blocks B_c and B_t, except for the B_t copy of GTF2IRD2 that appears to be a functional gene as well. Exons are depicted as black boxes, and the numbers indicate the first and last exons within the block. Numerical identification, location, and sequence difference of each site-specific nucleotide (SSN) that was used in this study are indicated and have been described previously.⁴ All dosage-analysis calculations were performed with regard to Patient 1, who carried one normal chromosome 7, and his father, who carried two normal chromosomes 7. The inferred recombinant block B in the duplicated chromosome is shown at the bottom. The predicted genotypes at each position are depicted as circles: white circles denote B_c-type, black circles B_m-type; and black-and-white circles either B_c-type or B_m-type. The region of exchange occurred somewhere between SSN 4 and SSN 6 within the NCF1 gene and one of its pseudogenes.

Patient 1 has a high and narrow forehead, a high and broad nose, a short philtrum, and facial asymmetry (Panel A). In Panel B, long eyelashes and retrognathia can be clearly seen.