De novostructural chromosomal imbalances: molecular cytogenetic characterization of partial trisomies

Abstract

De novo structural chromosomal imbalances represent a major challenge in modern cytogenetic diagnostics. Based solely on conventional cytogenetic techniques it may be impossible to identify the chromosomal origin of additional chromosomal material. In these cases molecular cytogenetic investigations including multicolor-FISH (M-FISH), spectral karyotyping (SKY), multicolor banding (MCB) and cenM-FISH combined with appropriate single-locus FISH probes are highly suitable for the determination of the chromosomal origin and fine characterization of derivative chromosomes. Here we report on four patients with de novo chromosomal imbalances and distinct chromosomal phenotypes, three of them harboring pure partial trisomies: a mildly affected boy with pure partial trisomy 10q22.2→q22.3∼23.1 due to an interstitial duplication, a girl with pure trisomy 12p11.21→pter and atypically moderate phenotype as the consequence of an X;autosome translocation, and a girl with multiple congenital abnormalities and severe developmental delay and a 46,XX,15p+ karyotype hiding a trisomy 17pter→17q11.1. The fourth patient is a girl with minor phenotypic features and mental retardation with an inverted duplication 18q10→p11.31 combined with a terminal deletion of 18p32. The clinical pictures are compared with previously described patients with focus on long term outcome.

The phenotype of recurrent 10q22q23 deletions and duplications

“…Precise genotype-phenotype correlations are hampered because these aberrations have often been detected by conventional cytogenetic techniques. In addition, except for one case reported by Dufke et al, 65 these duplications were much larger in size. Patients 9 and 12 displayed speech delay and impaired social interaction.…”

“…To date, only four cases overlapping this region have been reported. [64][65][66][67] Two of these patients had microcephaly and three had cardiac defects. Precise genotype-phenotype correlations are hampered because these aberrations have often been detected by conventional cytogenetic techniques.…”

Two de novo Overlapping Interstitial Duplications at 10q22 Associated with Speech Impairments, Behaviour Problems, Genital Anomalies, Developmental Delay and Intellectual Disability

“…To date, only eight patients with de novo deletions at 10q22 have been reported, and the main clinical features include speech impairments, dysmorphic features, genital anomalies, intellectual disability and developmental delay [7,[11][12][13][14][15]. Dufke and Han each described a case with a de novo duplication at 10q22.2q22.3~23.1 and 10q22q24 detected by G-banding analysis respectively, whereas the two segments not only covered the 10q22 region but also LCR3-4 which was demonstrated to be clinically significant [8][9][10]16,17]. Here, we report two unrelated patients with de novo overlapping duplications at the 10q22 interval that are 6.4 Mb and 9.8 Mb in size separately, detected by high-resolution CMA.…”

Prenatal detection of 10q22q23 duplications: dilemmas in phenotype prediction

“…Other anomalies including congenital heart defects, limb abnormalities, microcephaly, and hypotelorism have been observed in patients with duplications of varying sizes in this region. [6][7][8][9] Furthermore, incomplete penetrance has been demonstrated by the presence of duplication in a healthy mother of two affected children. 5 Therefore, despite the advancements in molecular genetic technology for detecting such genomic aberrations, the hindrance to interpreting duplications in the 10q22q23 region has not been removed.…”