title: 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.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01-211 Warszawa, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pietrzak
authors.forename: Kristin
authors.initials: K
authors.lastname: Mrasek
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Nadezda
authors.initials: N
authors.lastname: Kosyakova
authors.forename: Anja
authors.initials: A
authors.lastname: Weise
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Wei Wen
authors.initials: WW
authors.lastname: Cai
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Eggeling
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Mazurczak
authors.forename: Ewa
authors.initials: E
authors.lastname: Bocian
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
mesh_terms: D000782:Aneuploidy; D002675:Child, Preschool; D020223:Chromosome Painting; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D010641:Phenotype
chemical_list: D005819:Genetic Markers