De novo triplication of 11q12.3 in a patient with developmental delay and distinctive facial features

Abstract

BackgroundTriplication is a rare chromosomal anomaly. We identified a de novo triplication of 11q12.3 in a patient with developmental delay, distinctive facial features, and others. In the present study, we discuss the mechanism of triplications that are not embedded within duplications and potential genes which may contribute to the phenotype.ResultsThe identified triplication of 11q12.3 was 557 kb long and not embedded within the duplicated regions. The aberrant region was overlapped with the segment reported to be duplicated in 2 other patients. The common phenotypic features in the present patient and the previously reported patient were brain developmental delay, finger abnormalities (including arachnodactuly, camptodactyly, brachydactyly, clinodactyly, and broad thumbs), and preauricular pits.ConclusionsTriplications that are not embedded within duplicated regions are rare and sometimes observed as the consequence of non-allelic homologous recombination. The de novo triplication identified in the present study is novel and not embedded within the duplicated region. In the 11q12.3 region, many copy number variations were observed in the database. This may be the trigger of this rare triplication. Because the shortest region of overlap contained 2 candidate genes, STX5 and CHRM1, which show some relevance to neuronal functions, we believe that the genomic copy number gains of these genes may be responsible for the neurological features seen in these patients.

Breakpoint junction analysis for complex genomic rearrangements with the caldera volcano‐like pattern

“…As recurrent-tandem triplications can usually be generated by LCRs, this type of triplication can be observed in the known regions, including 7q11.2, 15q11, and Xp22.31 (Beunders et al, 2010;Castronovo et al, 2015;Liu et al, 2011). Based on our findings, exceptional cases of recurrent-tandem triplications, not embedded in duplication, are rare, and only two cases have thus far been reported; one of which is detailed in our previous findings (Al Dhaibani, Allingham-Hawkins, & El-Hattab, 2017;Yamamoto et al, 2013).…”

Longitudinal report of child with de novo 16p11.2 triplication

“…Copy number variation triplications are quite rare, and subsequently, the associated phenotype for 16p11.2 triplication is unknown. Reports of triplication at other loci indicate that triplication cases resemble duplication patients, including behavioral problems associated with 17q21.31 triplication and developmental delay associated with 11q12.3 . Although instances of triplication in 16p11.2 have been reported , this is the first study to report a comprehensive phenotype assessment on the developmental phenotype and trajectory of a child with a 16p11.2 triplication over a period of 4 years.…”

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

“…Genomic triplications are rare unbalanced chromosomal aberrations with variable clinical effects. [7][8][9][10] The association of triplication and segmental uniparental isodisomy (isoUPD) has been reported in only one single case. 8 Deciphering the mechanism of triplications has remained challenging because of the rarity of the events and the difficulty in defining the breakpoints with accuracy.…”