Molecular characterization of a new patient with a non‐recurrent inv dup del 2q and review of the mechanisms for this rearrangement

Abstract

We report on newborn baby with microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet. Cytogenetic studies revealed an inverted duplication with terminal deletion (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism. Microsatellite markers demonstrated that the inv dup del was maternal in origin and intrachromosomal. Intra or interchromosomal rearrangements may cause this aberration either by a U-type exchange (end-to-end fusion), an unequal crossover between inverted repeats (non-allelic homologous recombination: NAHR), or through breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non-homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined the breakpoints and did not detect a single copy region with a size exceeding 12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb, extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non-recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major clinical characteristics associated with this 2q rearrangement overlap with those commonly found in patients with 2q duplication reported in the literature.

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

“…A precise mapping of the deletions, however, was carried out in only a few studies (27/115 patients). [1][2][3][4][5][6][7][8][9][10]13,14,24,25,30,32 The patients with purely distal deletions (seven females, three males) included in the DECIPHER database (http://decipher.sanger.ac.uk/) had various deletion sizes ranging from 3 to 9.9 Mb. Unfortunately, clinical features were only mentioned for 2 of the 10 patients.…”

“…A precise mapping of the deleted regions is not often available, as most published cases have been characterized by conventional cytogenetics, subtelomeric fluorescence in situ hybridization (FISH) or microsatellite markers, and array-based comparative genomic hybridization (array-CGH) has only been used in a few studies. [1][2][3][4][5][6][7][8][9][10] At least 197 genes are located in the 2q37 region (230.7-243.2 Mb; Hg19; NCBI map viewer http://www.ncbi.nlm.nih.gov/mapview/). Of these, 11 have been reported as being potentially related to the 2q37-deletion phenotype so far, 5,[10][11][12][13][14][15][16][17] but the phenotypic implications of most of them remain unknown.…”

Phenotypic and Molecular Characterization of Partial Trisomy 2q Resulting from Insertion-Duplication in Chromosome 18q: A Case Report and Review of Literature

“…The clinical features were found to be associated with those found commonly in patients with 2q duplications, such as microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet [Vera-Carbonell et al, 2010].…”

“…Genotype and phenotype correlation was attempted by Vera-Carbonell et al [2010] in a patient with a 2q inverted duplicated segment of 38.75 Mb, spanning 2q33.1-q37.3, associated with a terminal deletion of 2.85 Mb, from 2q37.3 to the telomere. The clinical features were found to be associated with those found commonly in patients with 2q duplications, such as microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet [Vera-Carbonell et al, 2010].…”

Heterogeneity of a Constitutional Complex Chromosomal Rearrangement in 2q

“…Today, multiple molecular techniques such as array-based comparative genomic hybridization (array-CGH), bacterial artificial chromosome (BAC) FISH analyses, SNP oligonucleotide microarray, qPCR and whole-genome sequencing are the most useful techniques in order to characterize CCRs [López-Expósito et al, 2008;Wang et al, 2014;Macera et al, 2015;Wang et al, 2015]. It has been described that certain chromosomes, such as 1, 2, 5, 16, and 18, are prone to cause constitutional CCR [Houge et al, 2003;Vera-Carbonell et al, 2010;Genesio et al, 2013;Gu et al, 2013;Plaisancié et al, 2014;Wang et al, 2014;Gamba et al, 2015].…”