PMC

(a–d) G-banded partial karyotypes from Patients 1, 2, 3 and 4 with the normal chromosome (n) on the left and the duplicated (dup) or euchromatic variant (var) chromosome 16 on the right: (a) Patient 1 and (b) Patient 2 with the duplicated region of chromosome 16 indicated by the large black arrows; (c) Patient 3 and (d) Patient 4 with the euchromatic variant region of chromosome 16 indicated by the large black arrows. Note the similarity between the G-banded duplications in the Patients 1 and 2 (a, b) and the euchromatic variants in Patients 3 and 4 (c, d).

(a–e) The phenotype of Patient 1 aged 15 years: (a) Facial features showing heavy eyebrows, synophrys, slight ptosis, left convergent squint, broad nasal bridge, bow shaped upper lip and full lower lip; (b) lateral facial features showing overfolded helix, prominent glabella, upturned nose with a slightly bulbous tip and full everted lower lip; (c) oral features showing prominent upper incisors and dental crowding; (d) hands of the proband showing brachydactyly and squared off finger tips; and (e) feet of the proband showing bilateral medial protuberances near her ankles.

UCSC browser screenshot annotated with extent of the duplications, triplication, deletions and euchromatic variants of proximal 16p in the context of the UCSC browser bands and data on genomic variants and segmental duplications (NCBI 36/hg18): included are the 16p11.2–p21.2 duplications in Patients 1 and 2 (light grey bars), the 16p11.2–p21.2 duplications of Finelli et al (light grey bar), the 16p11.2–16p12.1 triplication (intermediate grey bar) and duplication (light grey bar) of Ballif et al,  subject 5, the duplications of Tabet et al, the reciprocal 16p11.2–p21.2 ‘micro'deletions (dark grey bar with narrow bars at either end indicating variable extent), the 16p12.1 microdeletions and duplications (diagonally hatched light and dark grey bars), the distal (formerly atypical) 16p11.2 microdeletions (dark grey bar), the common 16p11.2 microdeletions/duplications (diagonally hatched light and dark grey bars) and the euchromatic amplification variants in Patients 3 and 4 (dotted bars on a light grey background). The approximate start and end points of bands, imbalances, variants and candidate genes (CDR2, PLK1 and SH2B1) are given in Mb.

(a–f) Dual colour BAC FISH results and oaCGH results: (a) Distinct pairs of signals from RP11-142A12 (red arrows) indicating the duplication in Patient 2; (b) enh (large red arrow) and normal signals (small red arrow) with RP11-408D2 (red) consistent with amplification in a metaphase cell from Patient 3; (c) increased interval (blue arrows) between BAC RP11-67I10 (red) and the 16q11.2 microdissection probe (green) in a pair of chromosomes 16 from Patient 4; (d) enh (large red arrows) and normal signals (small red arrows) with RP11-408D2 (red) consistent with amplification in interphase and metaphase cells from Patient 4 (the centromeres of chromosomes 1, 5 and 19 have also been labelled in green in these images); (e) and (f) oaCGH results from Patients 1 (e) and 2 (f) analysed with the Agilent Analytics software. The vertical coloured bars and background represent the extent of the duplications adjacent to idiograms of chromosome 16 in the left hand panels, magnified in the right hand panels, with black dots representing oligonucleotides with normal copy number and red dots oligonucleotides with increased copy number. The colour reproduction of this figure is available at the European Journal of Human Genetics journal online.