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. 2018 Apr 27;11:26.
doi: 10.1186/s13039-018-0375-3. eCollection 2018.

Compound Phenotype in a Girl With r(22), Concomitant Microdeletion 22q13.32-q13.33 and Mosaic Monosomy 22

Free PMC article

Compound Phenotype in a Girl With r(22), Concomitant Microdeletion 22q13.32-q13.33 and Mosaic Monosomy 22

Anna A Kashevarova et al. Mol Cytogenet. .
Free PMC article


Background: Ring chromosome instability may influence a patient's phenotype and challenge its interpretation.

Results: Here, we report a 4-year-old girl with a compound phenotype. Cytogenetic analysis revealed her karyotype to be 46,XX,r(22). aCGH identified a 180 kb 22q13.32 duplication, a de novo 2.024 Mb subtelomeric 22q13.32-q13.33 deletion, which is associated with Phelan-McDermid syndrome, and a maternal single gene 382-kb TUSC7 deletion of uncertain clinical significance located in the region of the 3q13.31 deletion syndrome. All chromosomal aberrations were confirmed by real-time PCR in lymphocytes and detected in skin fibroblasts. The deletions were also found in the buccal epithelium. According to FISH analysis, 8% and 24% of the patient's lymphocytes and skin fibroblasts, respectively, had monosomy 22.

Conclusions: We believe that a combination of 22q13.32-q13.33 deletion and monosomy 22 in a portion of cells can better define the clinical phenotype of the patient. Importantly, the in vivo presence of monosomic cells indicates ring chromosome instability, which may favor karyotype correction that is significant for the development of chromosomal therapy protocols.

Keywords: Chromosome 22 monosomy; Compound phenotype; FAM19A5 gene; Phelan-McDermid syndrome; Ring chromosome 22.

Conflict of interest statement

The study was approved by the local Research Ethics Committee of the Research Institute of Medical Genetics, Tomsk NRMC. Written informed consent was obtained from the parents of the patient for her participation.Written informed consent was obtained from the parents of the patient for the publication of the clinical data and pictures.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Fig. 1
Fig. 1
The patient at 4 years of age (note plagiocephaly, high anterior hairline, broad forehead, epicanthus, widely spaced eyes, upslanted palpebral fissure, upper eyelid fullness, straight eyebrows, prominent ears, wide and depressed nasal bridge, bulbous nose, smooth and short philtrum, and thin vermillion of the upper lip)
Fig. 2
Fig. 2
Cytogenetic analysis. a Conventional cytogenetics analysis: ring chromosome 22; b FISH analysis with centromere-specific probes for chromosomes 14/22 (red) and a PCR-based probe for TBC1D22A (green) in cultured lymphocytes from the proband. The arrow indicates ring chromosome 22. C, D - FISH analysis with centromere-specific probes for chromosomes 14/22 (red) and PCR-based probes for TBC1D22A (green) in cultured skin fibroblasts from the proband. Ring chromosome 22 is designated by a white arrow (c); blue and pink arrows designate 46,XX,r(22) and 45,XX,-22 cells, respectively (d)
Fig. 3
Fig. 3
Molecular genetic analysis. a An aCGH image of chromosomes 3 and 22 in the lymphocytes of the patient. Deletions are designated by arrows. b Confirmation of the deletion at 22q13.32-q13.33 by quantitative real-time PCR analysis. c Confirmation of the deletion at 3q13.31 by quantitative real-time PCR analysis. d Identification of the deletions at 3q13.31 and 22q13.32-q13.33 in the buccal epithelium by quantitative real-time PCR analysis. e Confirmation of the duplication at 22q13.32 by quantitative real-time PCR analysis

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