Concurrence of ring 21 and trisomy 21 in children of normal parents

Abstract

We present a case of two siblings with different chromosome 21 abnormalities that are both de novo [r(21)/i(21p13) mosaicism and rob(14;21)]. Molecular studies using polymorphic markers have shown that these two aberrations had a common maternal origin. However, the parents were cytogenetically and phenotypically normal. This unusual association has not been reported and is considered to be a unique case that should be addressed.

Fig. 1

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, ×1000). (D) C-banding showing monocentric r(21) (arrow) and idic(21) (arrow-head) of the patient (×1000).

Fig. 2

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) (×1000).

Fig. 3

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.