Monosomy chromosome 21 compensated by 21q22.11q22.3 duplication in a case with small size and minor anomalies

Abstract

Background: Partial monosomy 21 is a rare finding with variable sizes and deletion breakpoints, presenting with a broad spectrum of phenotypes.

Case presentation: We report a 10-month-old boy with short stature, minor anomalies and mild motor delay. The patient had a monosomy 21 and duplication of the 21q22.11q22.3 region on the remaining derivative chromosome 21 which represents a partial 21q uniparental disomy of paternal origin, upd(21q22.11q22.3)pat. The abnormalities were characterized by karyotyping, FISH, chromosomal microarray, and genotyping.

Conclusions: This is the first case showing a monosomy 21 compensated by upd(21q22.11q22.3) as a mechanism of genomic rescue. Because there is no strong evidence showing imprinting on chromosome 21, the uniparental disomy itself is not associated with abnormal phenotype but has reduced phenotype severity of monosomy 21. We reviewed the previously published cases with isolated 21q deletions and identified a common deletion of 5.7 Mb associated with low birth weight, length and head circumference in the 21q21.2 region.

Keywords: Chromosome 21; Deletion; Duplication; Partial monosomy; Partial uniparental disomy.

Fig. 1

Clinical presentation and molecular cytogenetics analysis of the present patient. a Clinical presentation of the patient at 8 months of age. He had minor facial dysmorphic features including a broad, prominent forehead, mildly depressed nasal bridge, thin upper lip, small chin, and boarder-line low set ears. b-d Cytogenetic analysis identified a deletion and an AOH resulted by duplication in chromosome 21. b CGH and SNP array profile of chromosome 21. The numbers in the CGH pane are indicating log2 ratio of the intensity of fluorescence of the patient versus control genome. In the SNP pane, the numbers indicate the number of B allele. c Karyotype of the patient. d FISH analysis in both metaphase and interphase cells using probes designed for testing presence or absence of the 21q22.11q22.3 region (red). e Genotyping by Sanger sequencing indicating the paternal origin of the derivative chromosome 21. SNPs rs2776109 and rs68172960 (shown in red) are located in the 21q11.2q21.3 region, and rs6517210 and rs9968008 (shown in blue) covered the 21q22.11q22.3 UPD region. f Genomic location of the 21q deletions in the present patient and previously published cases. The red bar indicates the 15.98 Mb deletion at 21q11.2q21.3 (chr21:15,143,552_31,118,908, GRCh37/hg19) in our patient. The black bars represent the deletion regions of previously reported cases with isolated deletion at 21q overlapping with our patient, without any other chromosomal structural abnormality. Genomic locations are showed by UCSC genome browser