Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Abstract

Small supernumerary marker chromosomes (sSMCs) are a morphologically heterogeneous group of additional structurally abnormal chromosomes that cannot be identified unambiguously by conventional banding techniques alone. Molecular cytogenetic methods enable detailed characterization of sSMCs; however, in many cases interpretation of their clinical significance is problematic. The aim of our study was to characterize precisely sSMCs identified in three patients with dysmorphic features, psychomotor retardation and multiple congenital anomalies. We also attempted to correlate the patients' genotypes with phenotypes by inclusion of data from the literature. The sSMCs were initially detected by G-banding analysis in peripheral blood lymphocytes in these patients and were subsequently characterized using multicolor fluorescence in situ hybridization (M-FISH), (sub)centromere-specific multicolor FISH (cenM-FISH, subcenM-FISH), and multicolor banding (MCB) techniques. Additionally, the sSMCs in two patients were also studied by hybridization to whole-genome bacterial artificial chromosome (BAC) arrays (array-CGH) to map the breakpoints on a single BAC clone level. In all three patients, the chromosome origin, structure, and euchromatin content of the sSMCs were determined. In patient RS, only a neocentric r(2)(q35q36) was identified. It is a second neocentric sSMC(2) in the literature and the first marker chromosome derived from the terminal part of 2q. In the other two patients, two sSMCs were found, as M-FISH detected additional sSMCs that could not be characterized in G-banding analysis. In patient MK, each of four cell lines contained der(4)(:p11.1-->q12:) accompanied by a sSMC(18): r(18)(:p11.2-->q11.1::p11.2-->q11.1:), inv dup(18)(:p11.1-->q11.1::q11.1-->p11.1:), or der(18) (:p11.2-->q11.1::q11.1-->p11.1:). In patient NP, with clinical features of trisomy 8p, three sSMCs were characterized: r(8)(:p12-->q11.1::q11.1-->p21:) der(8) (:p11.22-->q11.1::q11.1-->p21::p21-->p11.22:) and der(21)(:p11.1-->q21.3:). The BAC array results confirmed the molecular cytogenetic results and refined the breakpoints to the single BAC clone resolution. However, the complex mosaic structure of the marker chromosomes derived from chromosomes 8 and 18 could only be identified by molecular cytogenetic methods. This study confirms the usefulness of multicolor FISH combined with whole-genome arrays for comprehensive analyses of marker chromosomes.

Tetrasomy 18p in a male dysmorphic child in southeast Turkey

“…Small supernumerary chromosomes (sSMC) of an unknown origin are commonly referred to as 'marker chromosomes' or 'ESACs' (extra structurally abnormal chromosomes) (Blennow et al 1993;Pietrzak et al 2007). They are found in an about 0.043% of the human population and have been estimated to result in an abnormal phenotype approximately 30% of sSMC carriers (Pietrzak et al 2007).…”

“…They are found in an about 0.043% of the human population and have been estimated to result in an abnormal phenotype approximately 30% of sSMC carriers (Pietrzak et al 2007).…”

A female infant case with tetrasomy 18p

“…Cases of Tetrasomy 18p may have variable phenotypic characteristics. The cause of different phenotypic features may be chromosomal origin, euchromatin content, mosaicism, parental origin and genomic imprinting 8 . Callen et al 9 suggested that parental age might be advanced in the isochromosome 18p syndrome.…”

Molecular Definition of High-resolution Multicolor Banding Probes: First Within the Human DNA Sequence Anchored FISH Banding Probe Set

“…In contrast to the standard aCGH, which uses dye reverse experiments as controls, there is no need for this when using microdissected DNA of interest because of the clear profiles at the expected regions. The rational of this approach was previously described for mapping of marker chromosome-derived DNA (Pietrzak et al 2007). …”