Molecular characterization of 20 small supernumerary marker chromosome cases using array comparative genomic hybridization and fluorescence in situ hybridization

Abstract

The variability of a small supernumerary marker chromosome (sSMC)-related phenotype is determined by the molecular component, the size, and shape of the marker chromosome. As fluorescence in situ hybridization has limitations regarding the resolution, efficiency, and accuracy. Recently, array comparative genomic hybridization (aCGH) was used for sSMC characterization. In this study, twenty cases with sSMCs were characterized by aCGH and FISH. Chromosomal origin of the marker chromosomes were successfully identified in seventeen of them. For the three cases with negative aCGH results, two of them were more likely due to that the sSMCs only contained centromere heterochromatin, whereas the reason for the remaining case with negative aCGH finding was uncertain. In order to establish a stronger genotype-phenotype correlation for clinical service in the future and avoid miss characterization, more sSMC cases were needed to be detailed characterized. This will help to clarify the variable clinical characteristics of sSMCs and provide additional information to aid clinical service and future research.

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

“…of sSMCs and detection of genomic copy number variations, chromosomal breakpoints and the genes involved (4,14). In the present study, CMA analysis detected a 0.44-Mb interstitial duplication in 6q25.3q26, which led to arr[hg19]6q2 5.3q26(160,569,492-161,010,647)x3.…”

“…sSMCs are defined as structurally abnormal chromosomes that may be detected in patients with developmental and/or mental retardation and infertility, and in prenatal or postnatal cases (21). The genotype-phenotype correlation of sSMC is currently complex and diverse due to its origin, size and constitution (14). Euchromatic sSMCs, encompassing gene dosage-sensitive genes, may be harmful, while sSMCs only containing heterochromatin are mostly harmless (22).…”

“…LPE 014R/G-A; spectrum: Red). The satellite III D15Z1 probe was located at 15p11.2 (spectrum: Green), the small nuclear ribonucleoprotein polypeptide N Prader-Willi/Angelman probe (SNRPN) was located at 15q11-q13 (spectrum: Orange) and the PML probe was located at 15q24 (spectrum: Orange) (14). All probes were supplied by Cytocell Technologies Ltd.…”

Molecular delineation of small supernumerary marker chromosomes using a single nucleotide polymorphism array

“…Case 3 presented an abnormal ultrasound indicating nasal bone hypoplasia and a mosaic karyotype of 47,XY, +mar [7] [32]. Neocentric sSMCs carry newly derived centromeres that are apparently formed within interstitial chromosomal sites and have no centromeric function, but it is unclear how the neocentromere is acquired and formed on an acentric fragment [33].…”

“…mental and growth retardation, craniofacial and urogenital abnormalities, and cardiac anomalies, which are associated with the size of the sSMCs, gene content, mosaicism percentage, uniparental disomy, and other concomitant imbalances [6]. Chromosomal microarray analysis is a sensitive technique for characterising sSMCs and can not only detect genomic copy number changes but also define breakpoints and the genes involved [7][8][9].…”