BRIEF REPORT |
Another Small Supernumerary Marker Chromosome (sSMC) Derived from Chromosome 2 : Towards a Genotype/Phenotype Correlation
Institute of Human Genetics and Anthropology, Jena, Germany
Correspondence to: Dr. Thomas Liehr, Institut für Humangenetik und Anthroplogie, Kollegiengasse 10, D-07743 Jena, Germany. E-mail: i8lith{at}mti.uni-jena.de
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Summary |
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Key Words: prenatal diagnosis FISH small supernumerary marker chromosome chromosome 2q genotype/phenotype correlation
A DEFINITION of small supernumerary marker chromosomes (sSMCs) was recently suggested as follows: "sSMC are structurally abnormal chromosomes that cannot be identified or characterized unambiguously by conventional banding cytogenetics alone, and are (in general) equal in size or smaller than a chromosome 20 of the same metaphase spread" (Liehr et al. 2004a). Therefore, sSMCs can be characterized only by molecular cytogenetic methods, i.e., fluorescence in situ hybridization (FISH). We recently proposed a strategy for how to proceed if a sSMC is detected (Liehr et al. 2003
,2004b
). According to that, apart from microdissection and reverse painting, the most straightforward way to determine an sSMC's origin is the cenM-FISH approach (Nietzel et al. 2001
). For characterization of the content and structure of the sSMC, the subcenM-FISH approach should be applied, as introduced and applied in
30 cases with sSMCs in Starke et al. (2003)
.
We followed that scheme in the case of a pregnant woman whose fetus after GTG-banding was found to have the karyotype 45,X[5]/47,XX,+mar[43]/46,XX[2]. The fetus was prenatally studied (amniocytic fluid in week 21+6) because it was an ICSI-induced pregnancy and, according to ultrasound examination, had a double bubble sign (i.e., sonographic signs of two cystic structures in the abdomen) and a single umbilical cord artery. The parents did not want a chromosome analysis of their own. Therefore, it could not be determined if the sSMC was inherited or had arisen de novo. The result of cenM-FISH (Figure 1) indicated that the marker was a small ring derived from chromosome 2. This result was confirmed and refined by subcenM-FISH (Figure 2). Therefore, the sSMC could be characterized as 47,XX,+r(2)(::p11.1->q11.2::). The pregnancy was continued and a healthy child was born. No Turner syndrome stigmata were present, and because the parents refused a postnatal chromosome analysis it could not be clarified if a Turner mosaic, as detected prenatally, was also present in the newborn.
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Five of the 11 cases reported in the literature and summarized in Table 1 are without clinical symptoms. However, only eight of those 11 cases were characterized in detail for their chromosomal content. Among those characterized comprehensively, there is a prominent correlation concerning presence of centromere-near sequences of 2p11.2 plus clinical abnormalities (cases 1 and 2) and absence of clinical signs plus presence of proximal sequences of 2q11.2 (cases 3, 4, and 5). Small partial trisomies of material derived distally from 2q11.2 already lead to clinical signs (cases 7 and 8). Case 6 has no clinical abnormalities and an sSMC similar to that of cases 7 and 8, but in case 6 there is no partial trisomy because a balanced karyotype 47,XY,del(2)(p10p12),+r(2)(::p10->q12::) was diagnosed. Therefore, we can speculate that case 9 consists of 2p centromeric and/or 2p11.2-derived material. Case 10 may include 2p11.2 or material distal from 2q11.2 and for case 11, for which the presence of 2q material is proven, the latter suggestion made for case 10 may also be true.
Even though uniparental disomy (UPD) must always be considered in case of an sSMC (Liehr et al. 2004a) and UPD 2 was excluded only for cases 5 and 8 in Table 1, we provide evidence for a first genotype/phenotype correlation of one small subgroup of sSMCs, those derived from chromosome 2 (Figure 3). It must be checked whether such a relatively simple correlation can be confirmed by further cases, e.g., for sSMC derived from chromosome 3 the situation seems to be more complex and is not yet resolved (Liehr et al. 2004c
).
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Acknowledgments |
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The case was kindly provided by Drs M. Kosskiewicz and H. Tittelbach (Nürnberg, Germany).
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Footnotes |
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Received for publication May 19, 2004; accepted August 30, 2004
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Literature Cited |
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