A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report
© Sheth et al; licensee BioMed Central Ltd. 2009
Received: 06 October 2009
Accepted: 12 November 2009
Published: 12 November 2009
Small supernumerary marker chromosomes (sSMC) can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar.
Here we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT) derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14)(q11.1). The present case is the third Turner syndrome case with an sSMCT not derived from the X- or the Y-chromosome.
More comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data.
Small supernumerary marker chromosomes (sSMC)  can be observed in a numerically normal 'basic karyotype', but also in numerically abnormal one like in a 'Turner-syndrome karyotype' (=sSMCT). At present 528 such cases with an sSMCT are reported [2, 3]. sSMCT are very rare in the common population (1:100000 ) - however, they can be observed 45 and even 60 times more frequent in infertile and developmentally and/or mentally retarded patients, respectively. The majority of sSMCT(X) form ring-chromosomes, while most sSMCT(Y) are inverted duplicated/isodicentric ones. When a mos 45,X/46,X,der(Y) or 45,X/46,XY is characterized it is important to counsel the patient concerning a possibility of gonadoblastoma and a preventive removal of gonadal tissue. In this connection, the necessity to apply molecular approaches for detection of cryptic 45,X/46,XY mosaicism is discussed, as a direct relationship between percentage of cells exhibiting a 45,X karyotype and patients phenotype does not exist. Additionally, it is a well-known fact that in a karyotype of mos 45,X/46,X,der(X) it is important to test for the ability of the der(X) to be inactivated, i.e. to test for the presence of the XIST-gene .
Here we report the third case with an sSMCT originating not from a gonosome but the first one proven to be derived from chromosome 14.
A ten year old girl was studied cytogenetically due to typical features of a Turner syndrome, i.e. short stature, webbing of neck, cubitus valgus, shield chest, congenital dislocation of hip, renal anomalies, clinodactyly, unilateral simian crease on right palm, acyanotic congenital heart disease and small patent ductus arteriosus.
Here we report the third case of a patient with sSMCT not derived from a gonosome. It is the first such case where the sSMC was characterized in detail by molecular cytogenetics and which turned out to be a de novo derivative of chromosome 14. Previously one case with a der(20)  and a not further specified sSMCT, however, proven to be not of gonosomal origin  were characterized. Overall, this is an interesting finding as neither chromosome 15 nor 22 were up to now identified as sSMCT, even though these two chromosomes are most frequently involved in sSMC formation [1, 3]. However, this might only be a bias due to only three known cases up to now. Furthermore, the exclusion of a uniparental disomy 14 would have been desirable; unfortunately no paternal material was available for that kind of study.
Among ~3.400 reported sSMC cases studied for their chromosomal origin and subsequently reported , by now 528 cases with sSMCT were found. Three of those sSMCT were not of gonosomal origin, i.e. 0.6%. However, the question is, if the percentage of this specific kind of sSMCT is not underestimated. Non-gonosomal sSMCT might be easily missed if they are not further characterized by molecular approaches.
In conclusion, a really comprehensive characterization of all sSMC by different probes, probe sets and approaches could enhance the detection rate of autosomal derived sSMCT.
Materials and methods
Metaphase chromosome preparations were obtained from PHA stimulated lymphocyte cultures according to standard procedures. Chromosome analysis was carried out applying GTG banding at a 600 band level according ISCN 2009  in the patient (25 metaphases) and both parents (50 metaphases, each).
Fluorescence in situ hybridization (FISH)
FISH was performed as previously reported . To characterize the sSMC first centromere specific multicolor FISH (cenM-FISH) and then subcentromere-specific M-FISH (subcenM-FISH) was performed; for details see . The here applied probe RP11-324B11 in 14q11.2 is located at 19,886,099-19,886,646 Mb.
Genomic DNA was extracted from peripheral blood lymphocytes using standard SDS-proteinase K extraction method . DNA concentration was determined with NanoDrop ND-1000 spectrophotometer and software (NanoDrop Technologies, Berlin, Germany). Detection of gene copy number was performed by array-Comparative Genomic Hybridization (array-CGH) experiments following standard and manufacturer's recommendations using 44.000 oligo probes approximately spaced at 40-100 kb intervals across the genome (Human Genome CGH microarray 44B kit, Agilent™). Male genomic DNA (Promega™) was used as reference in sex-match hybridizations which were analyzed with the CGH-analytics software v3.4 by applying Z-score segmentation algorithm with a window size of 10 points to identify chromosome aberrations. Analysis was performed with filter settings: 3-point filter and 0.2 of variation.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Supported in parts by the DAAD (D07/00070 and fellowship for ABH) and Prochance 2008 of the Friedrich Schiller University Jena 21007091 and Dept of Biotechnology (DBT) - BT/PR9111/MED/12/337/2007, India.
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