PMC2823026_01
The results of our cytogenetic studies. (A) The patient's karyotype was 46,XX,r(21)(p13q22.3) (ring 21 indicated by the empty arrow) and (B) 46,XX,idic(21)(p13) (isodicentric 21 indicated by the empty arrow-head). (C) The sister's karyotype was 46,XX,rob(14;21)(q10;q10),+21 (G-banding, x1000). (D) C-banding showing monocentric r(21) (arrow) and idic(21) (arrow-head) of the patient (x1000).
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F1
Cytogenetic analysis of peripheral lymphocytes with GTG banding revealed that the patient had a karyotype of 46,XX,r(21)(p13q22.3)[91]/46,XX, idic(21)(p13)[4]/46,XX[5] (Fig. 1A, B). Her elder sister had a karyotype of 46,XX,rob(14;21)(q10;q10),+21 (Fig. 1C). C-banding of the patient's chromosomes revealed that r(21) was monocentric and i(21) was dicentric (Fig. 1D).
Representative results of FISH analysis indicating r(21) and i(21) in the patient. (A) r(21): a single red signal of 21qter-specific probe on a normal chromosome 21 (white arrow), but no signal on an abnormal r(21) (white arrow-head). (B) The red signal of LSI21 is single on the normal chromosome 21, but is split on the abnormal i(21) (yellow arrow) (x1000).
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F2
FISH, performed using the AneuCyte  21 (21q22.2) unique sequence probe (Cytocell Ltd., Banbury, Oxfordshire, UK) and 21 telomere-specific probe (Q-biogene, Inc., Carlsbad, CA, USA), identified r(21) and i(21) each from different fields of the patient (Fig. 2A, B), and showed positive signals on the telomeric region of the maternal 21q (data not shown).
Comparison of the polymorphic markers used on the genomic DNA of the patient, her sister, and both parents. (A) The peak of an informative marker (D21S11) seen in the extra chromosome 21 of the sister (S) is the same as that of the mother, but the patient's peak cannot be readily traced back to the parental origin. (B) PCR products of the genomic DNA of the father (F), mother (M), and patient (P) are in the lanes on the right of the marker DNA. PCR analysis of two polymorphic markers (D21S1411 and D21S1446) was used to determine parental origin. The patient's product was consistent with that of the father, suggesting that the r(21) is of maternal origin.
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F3
Molecular studies using polymorphic markers (D7S820, D8S1179, D18S51, and D21S11) located on various chromosomes revealed that both children were of the same parentage and that the elder sister's extra chromosome 21 was of maternal origin (Fig. 3A). A maternal origin was determined for the r(21) of the patient, on the basis of DNA polymorphisms at the D21S1411 and D21S1446 loci (Fig. 3B).