BRIEF REPORT |
A Highly Complex Chromosomal Rearrangement between Five Chromosomes in a Healthy Female Diagnosed in Preparation for Intracytoplasmatic Sperm Injection
Institute of Human Genetics and Anthropology (AK,MZ,UC,TL), Department of Radiotherapy (AK), Friedrich-Schiller-University, Jena, Germany; Center of Human Genetics, University of Bremen, Bremen, Germany (CB,BR,JB); and Practice of Gynecology, Westoverledingen, Germany (JA)
Correspondence to: Dr. Alma Kuechler, Institute of Human Genetics and Anthropology, Kollegiengasse 10, D-07743 Jena, Germany. E-mail: almu{at}mti.uni-jena.de
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Summary |
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Key Words: complex chromosomal rearrangements 24-color fluorescence in situ hybridization multicolor banding intracytoplasmatic sperm injection
COMPLEX CHROMOSOMAL REARRANGEMENTS (CCR) involve by definition at least three chromosomes with three or more breakpoints. Most diagnosed CCRs are three-way rearrangements, and only a minority consists of highly complex aberrations (for review see Batanian and Eswara 1998; Houge et al. 2003
). CCR were subdivided by Kousseff et al. (1993)
into two groups based on the number of breaks (four or fewergroup I, more than four breaksgroup II). Following this suggestion, highly complex chromosomal rearrangements (hCCR) are herewith defined as CCR with five or more involved breakpoints. hCCRs are often associated with physical signs, mental retardation, or malformations. They are rarely found in phenotypically normal individuals and are usually detected in connection with reduced fertility, i.e., in- or subfertility in male carriers or recurrent miscarriages in female carriers (for review see Madan et al. 1997
). If fertility is maintained, the birth of a child with malformations can indicate familial occurrence of a CCR (Röthlisberger et al. 1999
; Berend et al. 2002
).
We report here on a clinically healthy, 34-year-old woman. She was referred for genetic diagnosis because of unwanted childlessness. Moreover, she had a history of two early abortions. Gynecological examination, including external and internal genitals and ovaries, and hormone status, were normal. Her partner was diagnosed with oligoasthenoteratozoospermia I. Therefore, use of an artificial reproductive technology was planned. In preparation for intracytoplasmatic sperm injection (ICSI), chromosome analysis was performed on both partners. The male had a normal karyotype [46,XY], but the GTG-banding results of the female showed a hCCR involving five chromosomes (chromosomes #3, #4, #7, #9, and #17, see Figure 1). These aberration occurred de novo as karyotype analyses of her parents showed no cytogenetic abnormalities.
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The rearrangement contained in summary six breakpoints derived from five chromosomes and seemed to be balanced on a molecular cytogenetic level. The hybridization results of 24-color FISH and MCB for all five aberrant chromosomes are depicted in Figure 3.
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As mentioned above, there are few cases of reported hCCR involving five or more chromosomes. The number of descriptions increased with the introduction of new techniques (Astbury et al. 2004), which also improved detection of intrachromosomal rearrangements (Weise et al. 2003
), but they remain rare findings. In our case, we detected in summary six breakpoints, all not located in known heterochromatic regions (such as 1q12 or centromeric regions). Thus, we speculate that all six breaks did not affect important genes or, more precisely, gene functions; however, this suspicion cannot be proven with the applied molecular cytogenetics approaches. Additionally, submicroscopic deletions or duplications close to the breakpoints could be excluded only by sequencing of the breakpoints.
The infertility of the couple, especially the history of two abortions, can easily be explained by the complexity of the hCCR itself and the extremely low probability of a cytogenetically balanced or normal pregnancy (Madan et al. 1997; Siffroi et al. 1997
). In such cases, the ICSI method also reaches its limits (Siffroi et al. 1997
), and careful genetic counseling of affected couples is required.
The lesson learned from this case is that, in preparation for ICSI, chromosome analysis should always be performed on both partners.
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Footnotes |
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Received for publication June 10, 2004; accepted November 19, 2004
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Literature Cited |
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