Figure 1
From: A deletion of FGFR2 creating a chimeric IIIb/IIIc exon in a child with Apert syndrome
Genome and sequence context of deletion in FGFR2. A. Schematic representation of FGFR2 around deleted region (red arrows); alternative splicing normally yields FGFR2b and FGFR2c spliceforms (yellow and turquoise lines respectively). Positions of previously described AS mutations are shown in blue; asterisks indicate recurrent missense mutations, downward arrows indicate Alu insertions, horizontal arrows represent the deletion. Other missense mutations of exons IIIa, IIIb and TM are not associated with AS (black asterisks). Intronic splicing enhancer/silencer (ISE/ISS) and exonic splicing silencer (ESS) elements are indicated with arrows (UISS - upstream intronic splicing silencer, DISS - downstream intronic splicing silencer, ISAR - intronic splicing activator and repressor). B. PCR of 2.5 kb region including exon IIIc, revealing a deletion in the patient (P) of ~1.4 kb compared to the control (C; N - negative control). Absence of normal-sized fragment in the patient sample is attributable to preferential amplification of the deleted allele. C. Sequence chromatogram of PCR products from 1B. The patient's chimeric exon is aligned with control exon IIIb and IIIc sequences. The 13 bp region of identity is shown between the red lines (fwd, forward and rvs, reverse sequence). D. Amino acid alignment of exons IIIb, IIIc, and the chimeric exon created by the deletion. Specific contacts for FGF10 and FGF2 are highlighted in yellow and turquoise respectively. Region of identity between exons is underlined.