19q13.33→qter trisomy in a girl with intellectual impairment and seizures

Abstract

Rearrangements in chromosome 19 are rare. Among the 35 patients with partial 19q trisomy described, only six have a breakpoint defined by array. The 19q duplication results in a variable phenotype, including dysmorphisms, intellectual disability and seizure. In a female patient, although G-banding at 550 band-resolution was normal, multiplex ligation-dependent probe amplification (MLPA) technique and genomic array showed a 10.6 Mb terminal duplication of chromosome 19q13. Fluorescent in situ hybridization (FISH) revealed that the duplicated region was attached to the short arm of chromosome 21 and silver staining showed four small acrocentrics with nucleolar organization region (NOR) activity, suggesting that the breakpoint in chromosome 21 was at p13. This is the first de novo translocation between 19q13.33 and 21p13 described in liveborn. The chromosome 19 is known to be rich in coding and non-coding regions, and chromosomal rearrangements involving this chromosome are very harmful. Furthermore, the 19q13.33→qter region is dense in pseudogenes and microRNAs, which are potent regulators of gene expression. The trisomic level of this region may contribute to deregulation of global gene expression, and consequently, may lead to abnormal development on the carriers of these rearrangements.

Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta

“…Duplications of 19q are rarely reported, perhaps due to the high transcriptional activity and gene content of this region [Forzano et al, ]. For duplications of the distal part of the long arm i.e., approximately 19q13.3 to the 19q telomere, the reported clinical features are intellectual disability, motor developmental delay, short stature, speech delay, seizures, short neck, and abnormal ears [Bhat et al, ; Lenzini et al, ; Resta et al, ; Carvalheira et al, ]. The phenotypic presentations reported in these patients involved craniofacial dysmorphia similar to Patient 1 and 2.…”

Duplications at 19q13.33 in patients with neurodevelopmental disorders

“…To identify additional CNVs absent in ClinVar and/or DECIPHER databases, we screened the literature and retrieved 3 additional studies, including 6 patients with duplications at the 19q13.33 locus. 11 – 13 All of these patients had seizures. Three patients carried CNVs of 1.22 Mb size, whereas the remaining 3 duplications were >10 Mb.…”

“…Blue horizontal bars represent the respective microduplication size and breakpoints according to GRCh37/hg19 human genome reference in a 12-Mb genomic window. Gray horizontal bars represent the respective microduplication reported in the study by Dorn et al 13 Carvalheira et al 11 and Wang et al 12 in which no exact copy number variant boundaries are specified (*). Microduplications larger than the depicted genomic interval are shown with arrows at boundaries (patients 1, 2, 7, and 8).…”

“…This is consistent with previous reports. 11 – 13 The consensus region overlapped 13 RefSeq genes ( figure, B ) that were further examined for brain expression, the presence of CNVs overlapping these genes in control cohorts, and variation intolerance ( table 2 ). Four genes persisted above all available filters, namely, the caspase recruitment domain family member 8 ( CARD8 ), the chromosome 19 open reading frame 68 ( C19orf68 ), the KDEL endoplasmic reticulum protein retention receptor 1 ( KDELR1 ), and the glutamate ionotropic receptor NMDA type subunit 2D ( GRIN2D ).…”

Three Offspring with Cri-du-Chat Syndrome from Phenotypically Normal Parents

“…The clinical features of our patients were correlated with CdCS, but in microarray analysis, we also found a 4.7-Mb duplication in chromosome 19q13.42q13.43. Terminal 19q13.3 duplications have been reported to be associated with neuromotor retardation, speech delay, epilepsy, short stature, abnormal ears, and short neck [Bhat et al, 2000;Resta et al, 2013;Carvalheira et al, 2014]. Two siblings who had a 4.3-Mb duplication in 19q13.42q13.43 (similar to our patients) with learning difficulties, short stature, dysmorphic facial features including hypertelorism, low set ears, and prominent chin, have been described, and it is suggested that these patients have clinical features similar to 19q terminal duplication reported previously [Balasubramanian et al, 2016].…”