( 2016, identifying 36 SNPs shared with the SNP array chip.īoth NGS data from the blood and the skin DNA samples were collected thus determining the genotypic layout in both tissues. To better evaluate the percentage of chimerism in P1 and P2, we are taking advantage of a 44‐Amplicon Custom Chimerism panel based on Ion AmpliSeq technology as previously reported by Aloisio et al. In both patients, log ratio appears normal, according with sex All BAF graph show a patchy chromosomal pattern due to an altered alignments of different allele‐combination segments. (b) Patient P2’s scattergrams relative to chromosome 1 and X. (a) Patient P1’s scattergrams relative to chromosome 1 and X. Scattergrams of B allele frequency (BAF) in single nucleotide polymorphism array analysis. This arrangement, although present also in P2, is more difficult to identify because of the strong quantitative imbalance of the two coexisting genomes (10:90%). This leads to a patchy BAF scattergram with four‐track interchanged with six‐track segments (Figure (Figure2a). Moreover, as shown in Figure Figure2a, 2a, we could observe that the AABB splits into two tracks because of the 30:70% of coexisting genomes. Although SNP array analysis shows a normal log ratio graph, the coexistence of two distinct genomes results in five different tracks (AAAA, AAAB, AABB, ABBB, BBBB) based on the number of allele combinations in autosomes. Quantification of alleles frequency on skin fibroblasts, demonstrated the presence of two genomes with frequency of 30:70% in P1 (Figure (Figure2a) 2a) and of 10:90%, in P2, respectively (Figure (Figure2b). Unexpectedly, the results showed a diffusely altered pattern of B allele frequencies (BAF) along all the autosomes that was consistent with the coexistence of two different genotypes with an altered ratio between the two haplotypes that could be explained by a chimeric status. However, since the clinical presentation of patients includes also cutaneous hypopigmented striae following Blaschko's line along the trunk (P1) and in the limbs (P2 Figure Figure1c), 1c), a SNP array analysis on DNA from skin biopsy was performed in order to investigate a mosaic condition. This study was approved by an ethics committee and patients gave written informed consent to the investigation, according to the Declaration of Helsinki. Subsequently, a custom next‐generation sequence (NGS) panel was used for chimerism quantification (Aloisio et al., 2016).īased on the whole clinical picture (see Supporting Information Appendix S1 Figure Figure1), 1), Patient 1 (female, P1) and Patient 2 (male, P2) underwent a classic and molecular (Human OmniExpress‐12 Bead Chip Illumina Inc., San Diego, USA) karyotyping on peripheral blood in order to study microdeletion/duplication and UPD involved in Silver–Russell (SRS) and Prader–Willi (PWS) syndromes. We discuss SNP array as a technique able to identify chimerism also suggesting which one of the complex mechanisms underlying chimera formation could be responsible (Biesecker & Spinner, 2013). ![]() Herein, we present two patients characterized by a Silver–Russell‐ and Prader–Willi‐like phenotypes in which, despite a genetically normal karyotype detected in blood, a genomewide single nucleotide polymorphism (SNP) array analysis on DNA from skin biopsies highlighted a chimeric status. About the origin of chimera individuals, four principal mechanisms have been identified as follows: (a) Tetragametic chimera (Green, Barton, Jenks, Pearson, & Yates, 1994) (b) Androgenetic chimera (Kaiser‐Rogers et al., 2006) (c) Fertilization of an ovum and a second polar body by two different spermatozoa and subsequent fusion of the two zygotes (Green et al., 1994) and (d) Parthenogenetic chimera (Giltay et al., 1998). All the other chimeric individuals would not be detectable by standard cytogenetic technology, suggesting that this phenomenon might be underdiagnosed. In phenotypically normal individuals, chimerism may come to light only if there is a reason to perform genetic testing, that is, blood typing discrepancy (Drexler et al., 2005) or paternity testing (Ramsay et al., 2009). Chimeras generally come to medical attention when they contain both male and female cells (46,XX/46,XY karyotype), causing disorders of sex development, or a discordance between external genitalia and chromosomal sex (Malan, Vekemans, & Turleau, 2006). The term “chimerism” refers to the presence of two or more genetically distinct cell lineages originating from different zygotes in the same individual and can be easily distinguished from mosaicism by the extent of genotypic differences along the genome.
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