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Case Reports
. 2021 Apr 16;12(4):581.
doi: 10.3390/genes12040581.

Mosaic Segmental and Whole-Chromosome Upd(11)mat in Silver-Russell Syndrome

Laura Pignata  1 , Angela Sparago  1 , Orazio Palumbo  2 , Elena Andreucci  3 , Elisabetta Lapi  3 , Romano Tenconi  4 , Massimo Carella  2 , Andrea Riccio  1   5 , Flavia Cerrato  1
Affiliations
Case Reports

Mosaic Segmental and Whole-Chromosome Upd(11)mat in Silver-Russell Syndrome

Laura Pignata et al. Genes (Basel). .

Abstract

Molecular defects altering the expression of the imprinted genes of the 11p15.5 cluster are responsible for the etiology of two congenital disorders characterized by opposite growth disturbances, Silver-Russell syndrome (SRS), associated with growth restriction, and Beckwith-Wiedemann syndrome (BWS), associated with overgrowth. At the molecular level, SRS and BWS are characterized by defects of opposite sign, including loss (LoM) or gain (GoM) of methylation at the H19/IGF2:intergenic differentially methylated region (H19/IGF2:IG-DMR), maternal or paternal duplication (dup) of 11p15.5, maternal (mat) or paternal (pat) uniparental disomy (upd), and gain or loss of function mutations of CDKN1C. However, while upd(11)pat is found in 20% of BWS cases and in the majority of them it is segmental, upd(11)mat is extremely rare, being reported in only two SRS cases to date, and in both of them is extended to the whole chromosome. Here, we report on two novel cases of mosaic upd(11)mat with SRS phenotype. The upd is mosaic and isodisomic in both cases but covers the entire chromosome in one case and is restricted to 11p14.1-pter in the other case. The segmental upd(11)mat adds further to the list of molecular defects of opposite sign in SRS and BWS, making these two imprinting disorders even more specular than previously described.

Keywords: Beckwith–Wiedemann syndrome; Silver–Russell syndrome; genomic imprinting; imprinting disorders; uniparental disomy.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Genetic characterization of the probands and their families. Left: pedigrees of the two families. Right: MS-MLPA results. CNVs (upper panels) and DNA methylation (lower panels) were analyzed at 10 imprinted loci, reported at the top of the figure. The mean values of seven control subjects were utilized for the assessment of relative copy number and methylation percentage. The purple arrows indicate the affected regions.
Figure 2
Figure 2
DNA methylation analysis of four DMRs performed on proband 1 and proband 2. Ctrl: average of three unaffected individuals.
Figure 3
Figure 3
SNP array analysis on genomic DNA of the two probands. Each panel represents the SNP array results of chromosome 11 only. The upper graphs indicate the copy number state; the lower graphs indicate the B allele frequency for each SNP. Note the differences presented by these two cases on the extent of upd, partial in proband 1 and complete in proband 2, and their level of mosaicism, which is higher for proband 1 (20%) than for proband 2 (∼10–15%).
See this image and copyright information in PMC

References

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