BRIEF REPORT |
Three Cases with Enlarged Acrocentric p-arms and Two Cases with Cryptic Partial Trisomies
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 acrocentric chromosomes p-arms FISH heteromorphism cryptic trisomy
WHEN an enlarged short arm of one of the acrocentric chromosomes (13, 14, 15, 21, and 22) is detected during karyotyping, the cytogeneticist must clarify whether this is due to an unusual variant or whether it masks a translocation event. Detection of such a p-arm variant is routinely followed by CBG and NOR staining and by karyotypic analysis of the parental chromosomes (Wyandt and Tonk 2004). Even though this usually leads to an informative result (Alitalo et al. 1988
; Schmid et al. 1994
; Reddy and Sulcova 1998
; Wyandt and Tonk 2004
) FISH (fluorescence in situ hybridization) techniques were introduced during the past decade to address that problem in more detail (e.g., Verma et al. 1996
). Especially for cases in which the p-arm enlargement hides a cryptic (euchromatic) rearrangement, molecular cytogenetics is crucial to characterize the chromosomal imbalance in detail (e.g., Morelli et al. 1999
; Benzacken et al. 2001
; Trifonov et al. 2003
).
Here we report on three cases with an enlarged p-arm in chromosome 13 (case 2 and 3) or 15 (case 1). Cases 1 and 3 were postnatal cases; case 3 was prenatal. Case 1 was a healthy adult male whose partner had a history of several abortions. Case 2 had a white spot detected in prenatal ultrasound screening. Case 3 was 2 years old and exhibited developmental delay, short stature, and several dysmorphic signs including blepharophimosis, high-arched palate, hypolastic philtrum, low-set ears, and microcephaly.
For cases 1 and 2 we applied the corresponding subcenM-FISH probe sets (Starke et al. 2003), and for case 3 the recently described acrocenM-FISH probe set (Trifonov et al. 2003
). Both probe sets contain the microdissection-derived probe midi54 specific for the short arm of all human acrocentric chromosomes (Mrasek et al. 2001
), which is essential for the characterization of p-arm heterochromatin presence or absence.
For case 1, the FISH result with the midi54 probe showed that the entire enlarged short arm consisted exclusively of heterochromatic material (Figure 1). Therefore, a balanced translocation was excluded as a reason for abortions in that family, although the large p-arm in one chromosome 15 could not be excluded as connection to that problem (i.e., mitotic problems during embryogenesis). Similar cases with such large p-arm variants and without phenotypic consequences were described previously (Wyandt and Tonk 2004). Especially for chromosome 15 p-arm variants, the possibility of a der(15)t(Y;15)(q12q11.2) must be considered (Alitalo et al. 1988
; Wyandt and Tonk 2004
).
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In summary, it can be assumed that every acrocentric short arm marker of which the size appears abnormally large should be studied in detail by different molecular cytogenetic methods such as M-FISH/SKY, microdissection, and reverse painting or cenM-FISH methods, including a probe such as midi54. In some cases the clinical phenotype may provide clues about the chromosomal region to look for (Benzacken et al. 2001), although in most cases, like those reported here, this advantage will not be present (Morelli et al. 1999
; Trifonov et al. 2003
).
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Acknowledgments |
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Cases were kindly provided by Dr Seidel (Jena), Dr Sandig (Weimar), and Dr Wegner (Berlin).
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Footnotes |
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Received for publication May 18, 2004; accepted June 7, 2004
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Literature Cited |
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