PMC5102301_01
Phenotypic features of the proband and the patient reported by Huret et al., and an illustration of the 21q21.2-q22.2 region highlighting the identified 2.78-Mb duplication and other reported segmental 21q duplication cases characterised by aCGH. (a-c) The proband at 5 years of age. Notable features include upslanting palpebral fissures, flat facies, prominent epicanthal folds and a flat nasal bridge. She also has bilateral single palmar creases and wide interspaces between the hallux and second digits on both feet. She has an ID, but lacks the 'happy personality' seen in many children with DS. Brachycephaly, protruding tongue and CHD were not present. (d) Oligonucleotide aCGH results of chromosome 21 in the proband. Coloured dots represent oligonucleotide aCGH probes plotted by their log2 ratios. The 2.78-Mb duplication at 21q22.11 is identifiable by the dense green probes with an average log2 ratio of ~0.6, indicating a single copy-number gain. (e) Chromosomal location of the 2.78-Mb duplication identified in the proband (light blue bar) compared with other reported interstitial copy-number aberrations characterised by aCGH with at least one breakpoint within 21q21.3-q22.2. Blue bands indicate duplications (partial trisomy), purple bands indicate triplications (partial tetrasomy) and red bands indicate deletions (partial monosomy). Black arrows indicate aberrations that extend proximally (left arrow) or distally (right arrow) beyond the limits of the region depicted in the figure. Genes previously identified as key critical genes in the overall DS phenotype are indicated by vertical pink translucent bars. (f) A French patient reported by Huret et al. in 1987 and photographed at 18 months of age has a similar facial appearance to our patient, lacked CHD and had a cytogenetically undetectable 21q duplication that likely involved SOD1 (see Discussion). Figure 1f reproduced from ref. 23 with permission from Springer, copyright 1987.
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Examination revealed a round, flat face with upslanting palpebral fissues, prominent epicanthae, flat nasal bridge (Figure 1a) and mild macroglossia. Hands were broad and small with mild bilateral fifth digit clinodactyly and bilateral single transverse palmar creases, and feet showed wide interspaces between first and second toes bilaterally (Figure 1b,c). Cytogenetic testing demonstrated a 46,XX normal female karyotype; however, aCGH detected a 2.78-Mb duplication of 21q22.11 (chr21:32,583,901-35,355,969; hg19) that included 16 genes (TIAM1, SOD1, HUNK, MRAP, URB1, SYNJ1, C21ORF59, OLIG2, OLIG1, IFNAR2, IFNAR1, GART, SON, DONSON, CRYZL1 and ITSN1; Figure 1d).